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- PDB-9o3w: Human 80S ribosome bound to IDB-001 stalled on MYC nascent chain -

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Basic information

Entry
Database: PDB / ID: 9o3w
TitleHuman 80S ribosome bound to IDB-001 stalled on MYC nascent chain
Components
  • (40S ribosomal protein ...) x 2
  • (60S ribosomal protein ...) x 3
  • (Large ribosomal subunit protein ...) x 37
  • (Small ribosomal subunit protein ...) x 29
  • (Ubiquitin-ribosomal protein ...) x 2
  • 18S rRNA
  • 28S rRNA
  • 5.8S rRNA
  • 5S rRNA
  • FAU ubiquitin-like and ribosomal protein S30
  • Nascent chain
  • P-site glutamyl-tRNA
  • Receptor of activated protein C kinase 1
  • mRNA
KeywordsTRANSLATION / translation inhibitor / interdictor / ribosome / cryogenic-electron microscopy (cryo-EM) / ribotoxic stress response / cancer / MYC
Function / homology
Function and homology information


embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex ...embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / axial mesoderm development / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / positive regulation of respiratory burst involved in inflammatory response / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / 90S preribosome assembly / positive regulation of DNA-templated transcription initiation / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / TNFR1-mediated ceramide production / alpha-beta T cell differentiation / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / negative regulation of RNA splicing / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / cytoplasmic translational initiation / NF-kappaB complex / negative regulation of DNA repair / G1 to G0 transition / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / ion channel inhibitor activity / laminin receptor activity / protein kinase A binding / Ribosomal scanning and start codon recognition / pigmentation / homeostatic process / positive regulation of mitochondrial depolarization / Translation initiation complex formation / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / Protein hydroxylation / monocyte chemotaxis / BH3 domain binding / negative regulation of translational frameshifting / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / SARS-CoV-1 modulates host translation machinery / positive regulation of GTPase activity / mTORC1-mediated signalling / TOR signaling / iron-sulfur cluster binding / regulation of cell division / Peptide chain elongation / cellular response to ethanol / Selenocysteine synthesis / Formation of a pool of free 40S subunits / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of protein binding / Eukaryotic Translation Termination / protein serine/threonine kinase inhibitor activity / blastocyst development / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / ubiquitin ligase inhibitor activity / negative regulation of respiratory burst involved in inflammatory response / Viral mRNA Translation / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of signal transduction by p53 class mediator / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus / negative regulation of ubiquitin-dependent protein catabolic process / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / protein targeting / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity
Similarity search - Function
40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L30e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / : ...40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L30e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / : / Ribosomal protein L23 / Ribosomal protein L2, archaeal-type / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / metallochaperone-like domain / TRASH domain / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / : / Ribosomal protein S12e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein S12e / Ribosomal protein L29e / Ribosomal L29e protein family / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein L13e / Ribosomal protein L13e / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Ribosomal protein S2, eukaryotic / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal protein L19, eukaryotic / : / Ribosomal protein L10e, conserved site / 40S Ribosomal protein S10 / Ribosomal protein L10e signature. / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19e signature. / Ribosomal protein L6e signature. / Ribosomal protein L44e signature. / 60S ribosomal protein L18a/ L20, eukaryotes / S27a-like superfamily / Ribosomal protein L10e / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein S30 / Ribosomal protein S30 / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein L23/L25, N-terminal / Ribosomal protein L23, N-terminal domain / : / : / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal L40e family / Ribosomal protein S7e signature. / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein L36e signature. / Ribosomal protein L30e signature 1. / Ribosomal protein L44e / Ribosomal protein L44 / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal protein L35Ae, conserved site / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal protein 60S L18 and 50S L18e / Ribosomal protein L35Ae signature. / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal_L40e / Ribosomal protein L40e / Ribosomal protein S17e, conserved site / Ribosomal protein L40e superfamily / Ribosomal protein S17e signature.
Similarity search - Domain/homology
: / : / 1,4-DIAMINOBUTANE / SPERMIDINE / : / : / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) ...: / : / 1,4-DIAMINOBUTANE / SPERMIDINE / : / : / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Small ribosomal subunit protein eS19 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL13 / Small ribosomal subunit protein eS27 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS10 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL34 / Large ribosomal subunit protein eL14 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein eL15 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein eL37 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein eL8 / Small ribosomal subunit protein eS4, X isoform / Large ribosomal subunit protein uL23 / Small ribosomal subunit protein eS6 / Large ribosomal subunit protein uL14 / Small ribosomal subunit protein uS19 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS25 / Small ribosomal subunit protein eS26 / Small ribosomal subunit protein eS28 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL2 / Small ribosomal subunit protein eS32 / Ubiquitin-ribosomal protein eS31 fusion protein / Ubiquitin-ribosomal protein eL40 fusion protein / Large ribosomal subunit protein eL38 / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein RACK1 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL42 / Large ribosomal subunit protein eL19 / Large ribosomal subunit protein eL20 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein eL18 / Large ribosomal subunit protein eL36
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 1.9 Å
AuthorsSauer, P.V. / Schuller, A.P. / Hamann, L.G.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2026
Title: Context-dependent translation inhibition as a cancer therapeutic modality.
Authors: Paige D Diamond / Paul V Sauer / Mikael Holm / Canessa J Swanson-Swett / Lucas Ferguson / Natalie M Bratset / Grant W Wienker / Justin Seiwert Sim / Hailey K Adams / Lillian Kenner / Margot ...Authors: Paige D Diamond / Paul V Sauer / Mikael Holm / Canessa J Swanson-Swett / Lucas Ferguson / Natalie M Bratset / Grant W Wienker / Justin Seiwert Sim / Hailey K Adams / Lillian Kenner / Margot Meyers / David Gygi / Zef A Könst / Sogole Sami Bahmanyar / Lawrence G Hamann / Anthony P Schuller /
Abstract: Recent work has demonstrated that some bacterial antibiotics that inhibit protein synthesis by binding the peptidyl transferase center (PTC) of the ribosome act in a context-dependent manner, ...Recent work has demonstrated that some bacterial antibiotics that inhibit protein synthesis by binding the peptidyl transferase center (PTC) of the ribosome act in a context-dependent manner, inhibiting translation elongation only at specific amino acids. However, this phenomenon has yet to be documented for compounds that inhibit the PTC of the human ribosome. Here, we use structure-based design to guide the synthesis of such PTC-binding, context-dependent inhibitors of the human ribosome, termed interdictors. In the PTC, these compounds preferentially interact with nascent protein residues that exhibit complementary physiochemical properties to the moieties of the small molecule, causing structural rearrangements in both the nascent polypeptide chain and ribosomal RNA. Further, the compounds differentially impact ribosome surveillance pathways, including the ribotoxic stress response. Finally, we confirm their anti-tumor activity after oral dosing in a mouse xenograft model of triple-negative breast cancer. Together, our data establish targeting oncogenic dependency factors through context-dependent inhibition of translation as a potential small molecule therapeutic modality for historically difficult to address cancers.
History
DepositionApr 7, 2025Deposition site: RCSB / Processing site: RCSB
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
L5: 28S rRNA
L7: 5S rRNA
L8: 5.8S rRNA
LA: 60S ribosomal protein L8
LB: Large ribosomal subunit protein uL3
LC: Large ribosomal subunit protein uL4
LD: Large ribosomal subunit protein uL18
LE: Large ribosomal subunit protein eL6
LF: 60S ribosomal protein L7
LG: Large ribosomal subunit protein eL8
LH: Large ribosomal subunit protein uL6
LI: Large ribosomal subunit protein uL16
LJ: Large ribosomal subunit protein uL5
LL: Large ribosomal subunit protein eL13
LM: Large ribosomal subunit protein eL14
LN: Large ribosomal subunit protein eL15
LO: Large ribosomal subunit protein uL13
LP: Large ribosomal subunit protein uL22
LQ: Large ribosomal subunit protein eL18
LR: Large ribosomal subunit protein eL19
LS: Large ribosomal subunit protein eL20
LT: Large ribosomal subunit protein eL21
LU: Large ribosomal subunit protein eL22
LV: Large ribosomal subunit protein uL14
LW: Large ribosomal subunit protein eL24
LX: Large ribosomal subunit protein uL23
LY: Large ribosomal subunit protein uL24
LZ: Large ribosomal subunit protein eL27
La: 60S ribosomal protein L27a
Lb: Large ribosomal subunit protein eL29
Lc: Large ribosomal subunit protein eL30
Ld: Large ribosomal subunit protein eL31
Le: Large ribosomal subunit protein eL32
Lf: Large ribosomal subunit protein eL33
Lg: Large ribosomal subunit protein eL34
Lh: Large ribosomal subunit protein uL29
Li: Large ribosomal subunit protein eL36
Lj: Large ribosomal subunit protein eL37
Lk: Large ribosomal subunit protein eL38
Ll: Large ribosomal subunit protein eL39
Lm: Ubiquitin-ribosomal protein eL40 fusion protein
Ln: Small ribosomal subunit protein eS32
Lo: Large ribosomal subunit protein eL42
Lp: Large ribosomal subunit protein eL43
Lr: Large ribosomal subunit protein eL28
NC: Nascent chain
Pt: P-site glutamyl-tRNA
S2: 18S rRNA
SA: Small ribosomal subunit protein uS2
SB: Small ribosomal subunit protein eS1
SC: Small ribosomal subunit protein uS5
SD: Small ribosomal subunit protein uS3
SE: Small ribosomal subunit protein eS4, X isoform
SF: Small ribosomal subunit protein uS7
SG: Small ribosomal subunit protein eS6
SH: Small ribosomal subunit protein eS7
SI: Small ribosomal subunit protein eS8
SJ: Small ribosomal subunit protein uS4
SK: Small ribosomal subunit protein eS10
SL: Small ribosomal subunit protein uS17
SM: Small ribosomal subunit protein eS12
SN: Small ribosomal subunit protein uS15
SO: Small ribosomal subunit protein uS11
SP: Small ribosomal subunit protein uS19
SQ: Small ribosomal subunit protein uS9
SR: Small ribosomal subunit protein eS17
SS: Small ribosomal subunit protein uS13
ST: Small ribosomal subunit protein eS19
SU: Small ribosomal subunit protein uS10
SV: 40S ribosomal protein S21
SW: Small ribosomal subunit protein uS8
SX: Small ribosomal subunit protein uS12
SY: 40S ribosomal protein S24
SZ: Small ribosomal subunit protein eS25
Sa: Small ribosomal subunit protein eS26
Sb: Small ribosomal subunit protein eS27
Sc: Small ribosomal subunit protein eS28
Sd: Small ribosomal subunit protein uS14
Se: FAU ubiquitin-like and ribosomal protein S30
Sf: Ubiquitin-ribosomal protein eS31 fusion protein
Sg: Receptor of activated protein C kinase 1
mR: mRNA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)4,102,280655
Polymers4,082,83582
Non-polymers19,445573
Water130,7717259
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

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RNA chain , 6 types, 6 molecules L5L7L8PtS2mR

#1: RNA chain 28S rRNA


Mass: 1640884.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
#2: RNA chain 5S rRNA


Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 23898
#3: RNA chain 5.8S rRNA


Mass: 50171.703 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 555853
#47: RNA chain P-site glutamyl-tRNA


Mass: 24136.328 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
#48: RNA chain 18S rRNA


Mass: 603580.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
#82: RNA chain mRNA


Mass: 268011.844 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)

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60S ribosomal protein ... , 3 types, 3 molecules LALFLa

#4: Protein 60S ribosomal protein L8 / Large ribosomal subunit protein uL2


Mass: 28088.863 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62917
#9: Protein 60S ribosomal protein L7 / Large ribosomal subunit protein uL30


Mass: 29290.973 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P18124
#29: Protein 60S ribosomal protein L27a / Large ribosomal subunit protein uL15


Mass: 16604.535 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46776

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Large ribosomal subunit protein ... , 37 types, 37 molecules LBLCLDLELGLHLILJLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLbLcLdLeLfLgLh...

#5: Protein Large ribosomal subunit protein uL3 / 60S ribosomal protein L3 / HIV-1 TAR RNA-binding protein B / TARBP-B


Mass: 46224.133 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P39023
#6: Protein Large ribosomal subunit protein uL4 / 60S ribosomal protein L4 / 60S ribosomal protein L1


Mass: 47804.621 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P36578
#7: Protein Large ribosomal subunit protein uL18 / 60S ribosomal protein L5


Mass: 34426.789 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46777
#8: Protein Large ribosomal subunit protein eL6 / 60S ribosomal protein L6 / Neoplasm-related protein C140 / Tax-responsive enhancer element-binding ...60S ribosomal protein L6 / Neoplasm-related protein C140 / Tax-responsive enhancer element-binding protein 107 / TaxREB107


Mass: 32810.176 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q02878
#10: Protein Large ribosomal subunit protein eL8 / 60S ribosomal protein L7a / PLA-X polypeptide / Surfeit locus protein 3


Mass: 30061.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62424
#11: Protein Large ribosomal subunit protein uL6 / 60S ribosomal protein L9


Mass: 21899.471 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P32969
#12: Protein Large ribosomal subunit protein uL16 / 60S ribosomal protein L10 / Laminin receptor homolog / Protein QM / Ribosomal protein L10 / Tumor ...60S ribosomal protein L10 / Laminin receptor homolog / Protein QM / Ribosomal protein L10 / Tumor suppressor QM


Mass: 24630.061 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P27635
#13: Protein Large ribosomal subunit protein uL5 / 60S ribosomal protein L11 / CLL-associated antigen KW-12


Mass: 20288.465 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62913
#14: Protein Large ribosomal subunit protein eL13 / 60S ribosomal protein L13 / Breast basic conserved protein 1


Mass: 24321.682 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P26373
#15: Protein Large ribosomal subunit protein eL14 / 60S ribosomal protein L14 / CAG-ISL 7


Mass: 23485.016 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P50914
#16: Protein Large ribosomal subunit protein eL15 / 60S ribosomal protein L15


Mass: 24207.285 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61313
#17: Protein Large ribosomal subunit protein uL13 / 60S ribosomal protein L13a / 23 kDa highly basic protein


Mass: 23633.412 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P40429
#18: Protein Large ribosomal subunit protein uL22 / 60S ribosomal protein L17 / 60S ribosomal protein L23 / PD-1


Mass: 21443.170 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P18621
#19: Protein Large ribosomal subunit protein eL18 / 60S ribosomal protein L18


Mass: 21687.676 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q07020
#20: Protein Large ribosomal subunit protein eL19 / 60S ribosomal protein L19


Mass: 23535.281 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P84098
#21: Protein Large ribosomal subunit protein eL20 / 60S ribosomal protein L18a


Mass: 20808.514 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q02543
#22: Protein Large ribosomal subunit protein eL21 / 60S ribosomal protein L21


Mass: 18609.988 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46778
#23: Protein Large ribosomal subunit protein eL22 / 60S ribosomal protein L22 / EBER-associated protein / EAP / Epstein-Barr virus small RNA-associated ...60S ribosomal protein L22 / EBER-associated protein / EAP / Epstein-Barr virus small RNA-associated protein / Heparin-binding protein HBp15


Mass: 14813.015 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P35268
#24: Protein Large ribosomal subunit protein uL14 / 60S ribosomal protein L23 / 60S ribosomal protein L17


Mass: 14892.505 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62829
#25: Protein Large ribosomal subunit protein eL24 / 60S ribosomal protein L24 / 60S ribosomal protein L30


Mass: 17825.111 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P83731
#26: Protein Large ribosomal subunit protein uL23 / 60S ribosomal protein L23a


Mass: 17740.193 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62750
#27: Protein Large ribosomal subunit protein uL24 / 60S ribosomal protein L26


Mass: 17303.363 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61254
#28: Protein Large ribosomal subunit protein eL27 / 60S ribosomal protein L27


Mass: 15835.831 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61353
#30: Protein Large ribosomal subunit protein eL29 / 60S ribosomal protein L29 / Cell surface heparin-binding protein HIP


Mass: 17817.295 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P47914
#31: Protein Large ribosomal subunit protein eL30 / 60S ribosomal protein L30


Mass: 12805.092 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62888
#32: Protein Large ribosomal subunit protein eL31 / 60S ribosomal protein L31


Mass: 14494.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62899
#33: Protein Large ribosomal subunit protein eL32 / 60S ribosomal protein L32


Mass: 15898.932 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62910
#34: Protein Large ribosomal subunit protein eL33 / 60S ribosomal protein L35a / Cell growth-inhibiting gene 33 protein


Mass: 12564.743 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P18077
#35: Protein Large ribosomal subunit protein eL34 / 60S ribosomal protein L34


Mass: 13326.074 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P49207
#36: Protein Large ribosomal subunit protein uL29 / 60S ribosomal protein L35


Mass: 14593.624 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P42766
#37: Protein Large ribosomal subunit protein eL36 / 60S ribosomal protein L36


Mass: 12290.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9Y3U8
#38: Protein Large ribosomal subunit protein eL37 / 60S ribosomal protein L37 / G1.16


Mass: 11111.032 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61927
#39: Protein Large ribosomal subunit protein eL38 / 60S ribosomal protein L38


Mass: 8238.948 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63173
#40: Protein Large ribosomal subunit protein eL39 / 60S ribosomal protein L39


Mass: 6426.759 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62891
#43: Protein Large ribosomal subunit protein eL42 / 60S ribosomal protein L36a / 60S ribosomal protein L44 / Cell growth-inhibiting gene 15 protein / ...60S ribosomal protein L36a / 60S ribosomal protein L44 / Cell growth-inhibiting gene 15 protein / Cell migration-inducing gene 6 protein


Mass: 12489.991 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P83881
#44: Protein Large ribosomal subunit protein eL43 / 60S ribosomal protein L37a


Mass: 10299.350 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61513
#45: Protein Large ribosomal subunit protein eL28 / 60S ribosomal protein L28


Mass: 15679.466 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46779

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Ubiquitin-ribosomal protein ... , 2 types, 2 molecules LmSf

#41: Protein Ubiquitin-ribosomal protein eL40 fusion protein / CEP52 / Ubiquitin A-52 residue ribosomal protein fusion product 1


Mass: 14800.474 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62987
#80: Protein Ubiquitin-ribosomal protein eS31 fusion protein / Ubiquitin carboxyl extension protein 80


Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979

+
Small ribosomal subunit protein ... , 29 types, 29 molecules LnSASBSCSDSESFSGSHSISJSKSLSMSNSOSPSQSRSSSTSUSWSXSZSaSbScSd

#42: Protein/peptide Small ribosomal subunit protein eS32 / 60S ribosomal protein L41 / HG12 / Large ribosomal subunit protein eL41


Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62945
#49: Protein Small ribosomal subunit protein uS2 / 37 kDa laminin receptor precursor / 37LRP / 37/67 kDa laminin receptor / LRP/LR / 40S ribosomal ...37 kDa laminin receptor precursor / 37LRP / 37/67 kDa laminin receptor / LRP/LR / 40S ribosomal protein SA / 67 kDa laminin receptor / 67LR / Colon carcinoma laminin-binding protein / Laminin receptor 1 / LamR / Laminin-binding protein precursor p40 / LBP/p40 / Multidrug resistance-associated protein MGr1-Ag / NEM/1CHD4


Mass: 32778.777 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P08865
#50: Protein Small ribosomal subunit protein eS1 / 40S ribosomal protein S3a / v-fos transformation effector protein / Fte-1


Mass: 30002.061 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61247
#51: Protein Small ribosomal subunit protein uS5 / 40S ribosomal protein S2 / 40S ribosomal protein S4 / Protein LLRep3


Mass: 31376.516 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P15880
#52: Protein Small ribosomal subunit protein uS3 / 40S ribosomal protein S3


Mass: 26729.369 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
References: UniProt: P23396, DNA-(apurinic or apyrimidinic site) lyase
#53: Protein Small ribosomal subunit protein eS4, X isoform / 40S ribosomal protein S4 / SCR10 / Single copy abundant mRNA protein


Mass: 29654.869 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62701
#54: Protein Small ribosomal subunit protein uS7 / 40S ribosomal protein S5


Mass: 22913.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46782
#55: Protein Small ribosomal subunit protein eS6 / 40S ribosomal protein S6 / Phosphoprotein NP33


Mass: 28751.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62753
#56: Protein Small ribosomal subunit protein eS7 / 40S ribosomal protein S7


Mass: 22168.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62081
#57: Protein Small ribosomal subunit protein eS8 / 40S ribosomal protein S8


Mass: 24263.387 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62241
#58: Protein Small ribosomal subunit protein uS4 / 40S ribosomal protein S9


Mass: 22641.564 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46781
#59: Protein Small ribosomal subunit protein eS10 / 40S ribosomal protein S10


Mass: 18933.846 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46783
#60: Protein Small ribosomal subunit protein uS17 / 40S ribosomal protein S11


Mass: 18468.826 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62280
#61: Protein Small ribosomal subunit protein eS12 / 40S ribosomal protein S12


Mass: 14538.987 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P25398
#62: Protein Small ribosomal subunit protein uS15 / 40S ribosomal protein S13


Mass: 17259.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62277
#63: Protein Small ribosomal subunit protein uS11 / 40S ribosomal protein S14


Mass: 16302.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62263
#64: Protein Small ribosomal subunit protein uS19 / 40S ribosomal protein S15 / RIG protein


Mass: 17076.207 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62841
#65: Protein Small ribosomal subunit protein uS9 / 40S ribosomal protein S16


Mass: 16477.377 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62249
#66: Protein Small ribosomal subunit protein eS17 / 40S ribosomal protein S17


Mass: 15578.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P08708
#67: Protein Small ribosomal subunit protein uS13 / 40S ribosomal protein S18 / Ke-3 / Ke3


Mass: 17759.777 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62269
#68: Protein Small ribosomal subunit protein eS19 / 40S ribosomal protein S19


Mass: 16091.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P39019
#69: Protein Small ribosomal subunit protein uS10 / 40S ribosomal protein S20


Mass: 13398.763 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P60866
#71: Protein Small ribosomal subunit protein uS8 / 40S ribosomal protein S15a


Mass: 14865.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62244
#72: Protein Small ribosomal subunit protein uS12 / 40S ribosomal protein S23


Mass: 15860.666 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62266
#74: Protein Small ribosomal subunit protein eS25 / 40S ribosomal protein S25


Mass: 13776.224 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62851
#75: Protein Small ribosomal subunit protein eS26 / 40S ribosomal protein S26


Mass: 13047.532 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62854
#76: Protein Small ribosomal subunit protein eS27 / 40S ribosomal protein S27 / Metallopan-stimulin 1 / MPS-1


Mass: 9480.186 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P42677
#77: Protein Small ribosomal subunit protein eS28 / 40S ribosomal protein S28


Mass: 7855.052 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62857
#78: Protein Small ribosomal subunit protein uS14 / 40S ribosomal protein S29


Mass: 6690.821 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62273

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Protein/peptide , 1 types, 1 molecules NC

#46: Protein/peptide Nascent chain


Mass: 1884.049 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: fusion protein FLAG-VHP-MYC: DYKDDDDKDYKDDDDKDYKDDDDKGSLSDEDFKAVFGMTRSAFANLPLWKQQNLKKEKGLFGSSPQGSPEPLVLHEETPPTTSSDSEEEQEDE
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)

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40S ribosomal protein ... , 2 types, 2 molecules SVSY

#70: Protein 40S ribosomal protein S21 / Small ribosomal subunit protein eS21


Mass: 9150.427 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63220
#73: Protein 40S ribosomal protein S24 / Small ribosomal subunit protein eS24


Mass: 15463.333 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62847

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Protein , 2 types, 2 molecules SeSg

#79: Protein FAU ubiquitin-like and ribosomal protein S30


Mass: 14415.724 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62861
#81: Protein Receptor of activated protein C kinase 1 / Cell proliferation-inducing gene 21 protein / Guanine nucleotide-binding protein subunit beta-2- ...Cell proliferation-inducing gene 21 protein / Guanine nucleotide-binding protein subunit beta-2-like 1 / Guanine nucleotide-binding protein subunit beta-like protein 12.3 / Human lung cancer oncogene 7 protein / HLC-7 / Receptor for activated C kinase / Small ribosomal subunit protein RACK1


Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244

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Non-polymers , 8 types, 7832 molecules

#83: Chemical...
ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 170 / Source method: obtained synthetically / Formula: K
#84: Chemical
ChemComp-PUT / 1,4-DIAMINOBUTANE / PUTRESCINE


Mass: 88.151 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C4H12N2
#85: Chemical
ChemComp-SPD / SPERMIDINE / N-(2-AMINO-PROPYL)-1,4-DIAMINOBUTANE / PA(34)


Mass: 145.246 Da / Num. of mol.: 14 / Source method: obtained synthetically / Formula: C7H19N3
#86: Chemical ChemComp-A1B75 / (2R,3S,4S)-4-hydroxy-2-[(4-methoxyphenyl)methyl]pyrrolidin-3-yl {2-[(2S)-pyrrolidin-2-yl]ethyl}carbamate


Mass: 363.451 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H29N3O4 / Feature type: SUBJECT OF INVESTIGATION
#87: Chemical ChemComp-TRS / 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / TRIS BUFFER


Mass: 122.143 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C4H12NO3 / Comment: pH buffer*YM
#88: Chemical...
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 371 / Source method: obtained synthetically / Formula: Mg
#89: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Zn
#90: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 7259 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY
Has protein modificationY
Sequence detailsThe full sequence of Nascent chain is ...The full sequence of Nascent chain is DYKDDDDKDYKDDDDKDYKDDDDKGSLSDEDFKAVFGMTRSAFANLPLWKQQNLKKEKGLFGSSPQGSPEPLVLHEETPPTTSSDSEEEQEDE

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Human 80S ribosome bound to IDB-001 stalled on MYC nascent chain
Type: RIBOSOME / Entity ID: #46, #1-#44, #47-#48, #50-#82 / Source: NATURAL
Molecular weightValue: 4.3 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
Details: 20mM Tris, 100mM KOAc, 7.5mM MgOAc, 0.25mM Spermidine, 2mM DTT, 0.05% w/v b-OG, 50uM IDB-001
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid type: Quantifoil
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 292 K

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 900 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2PHENIX1.21.2_5419model refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 1.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 538472 / Symmetry type: POINT

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