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- PDB-6olz: Human ribosome nascent chain complex (PCSK9-RNC) stalled by a dru... -

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Basic information

Entry
Database: PDB / ID: 6olz
TitleHuman ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like molecule with PP tRNA
Components
  • (40S ribosomal protein ...) x 31
  • (60S ribosomal protein ...) x 42
  • 18S ribosomal RNA
  • 28S ribosomal RNA
  • 5.8S ribosomal RNA
  • 5S ribosomal RNA
  • Proprotein convertase subtilisin/kexin type 9
  • Receptor of activated protein C kinase 1
  • Ubiquitin-40S ribosomal protein S27a
  • mRNA
  • tRNA
KeywordsRIBOSOME / selective stalling / drug-like molecule / human ribosome nascent chain complex
Function / homology
Function and homology information


adenylosuccinate lyase / N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity / (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity / eukaryotic 80S initiation complex / : / negative regulation of protein neddylation / 'de novo' AMP biosynthetic process / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding ...adenylosuccinate lyase / N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity / (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity / eukaryotic 80S initiation complex / : / negative regulation of protein neddylation / 'de novo' AMP biosynthetic process / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / ribosomal protein import into nucleus / embryonic brain development / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / oxidized purine DNA binding / neural crest cell differentiation / NF-kappaB complex / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / negative regulation of phagocytosis / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / A band / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / alpha-beta T cell differentiation / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of G1 to G0 transition / exit from mitosis / laminin receptor activity / pigmentation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / 'de novo' IMP biosynthetic process / optic nerve development / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / Translation initiation complex formation / retinal ganglion cell axon guidance / fibroblast growth factor binding / mammalian oogenesis stage / homeostatic process / positive regulation of mitochondrial depolarization / G1 to G0 transition / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / negative regulation of Wnt signaling pathway / lung morphogenesis / negative regulation of peptidyl-serine phosphorylation / iron-sulfur cluster binding / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / regulation of cell division / BH3 domain binding / cysteine-type endopeptidase activator activity involved in apoptotic process / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / blastocyst development / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / negative regulation of respiratory burst involved in inflammatory response / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein localization to nucleus / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit
Similarity search - Function
Adenylosuccinate lyase PurB, C-terminal / : / Adenylosuccinate lyase C-terminal / Adenylosuccinate lyase / Fumarate lyase, conserved site / Fumarate lyases signature. / Fumarate lyase family / Fumarate lyase, N-terminal / Lyase / Fumarase/histidase, N-terminal ...Adenylosuccinate lyase PurB, C-terminal / : / Adenylosuccinate lyase C-terminal / Adenylosuccinate lyase / Fumarate lyase, conserved site / Fumarate lyases signature. / Fumarate lyase family / Fumarate lyase, N-terminal / Lyase / Fumarase/histidase, N-terminal / L-Aspartase-like / 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 protein L2, archaeal-type / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / Ribosomal protein L18e / Ribosomal protein 60S L18 and 50S L18e / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / metallochaperone-like domain / TRASH domain / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein L14 / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein S21e / Ribosomal protein L13e, conserved site / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein L13e signature. / Ribosomal protein S2, eukaryotic / Small (40S) ribosomal subunit Asc1/RACK1 / S27a-like superfamily / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / 40S Ribosomal protein S10 / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L44e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L10e / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein L13e / Ribosomal protein S2, eukaryotic/archaeal / Ribosomal protein L13e / Ribosomal protein L19, eukaryotic / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein S30 / : / : / Ribosomal protein S30 / 60S ribosomal protein L18a/ L20, eukaryotes / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein S7e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19e signature. / Ribosomal protein L24e signature. / Ribosomal protein S3, eukaryotic/archaeal / Ribosomal protein L44e / Ribosomal protein L44 / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / :
Similarity search - Domain/homology
Chem-MVM / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / FAU ubiquitin like and ribosomal protein S30 fusion / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein eL33 ...Chem-MVM / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / FAU ubiquitin like and ribosomal protein S30 fusion / 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 eS4, Y isoform 1 / 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 / : / 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 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 / Adenylosuccinate lyase / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein eL36
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsLi, W. / Cate, J.H.D.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)R01-GM065050 United States
CitationJournal: Nat Struct Mol Biol / Year: 2019
Title: Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule.
Authors: Wenfei Li / Fred R Ward / Kim F McClure / Stacey Tsai-Lan Chang / Elizabeth Montabana / Spiros Liras / Robert G Dullea / Jamie H D Cate /
Abstract: The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ...The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest.
History
DepositionApr 17, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 19, 2019Provider: repository / Type: Initial release
Revision 1.1Dec 18, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization

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Structure visualization

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Assembly

Deposited unit
AA: 60S ribosomal protein L8
BA: 40S ribosomal protein SA
AB: 60S ribosomal protein L3
BB: 40S ribosomal protein S3a
AC: 60S ribosomal protein L4
BC: 40S ribosomal protein S2
A3: 5.8S ribosomal RNA
A4: 5S ribosomal RNA
AD: 60S ribosomal protein L5
AE: 60S ribosomal protein L6
AF: 60S ribosomal protein L7
AG: 60S ribosomal protein L7a
AH: 60S ribosomal protein L9
AI: 60S ribosomal protein L10
AJ: 60S ribosomal protein L11
AL: 60S ribosomal protein L13
AM: 60S ribosomal protein L14
AN: 60S ribosomal protein L15
AO: 60S ribosomal protein L13a
AP: 60S ribosomal protein L17
AQ: 60S ribosomal protein L18
AR: 60S ribosomal protein L19
AS: 60S ribosomal protein L18a
AT: 60S ribosomal protein L21
AU: 60S ribosomal protein L22
AV: 60S ribosomal protein L23
AW: 60S ribosomal protein L24
AX: 60S ribosomal protein L23a
AY: 60S ribosomal protein L26
AZ: 60S ribosomal protein L27
Aa: 60S ribosomal protein L27a
Ab: 60S ribosomal protein L29
Ac: 60S ribosomal protein L30
Ad: 60S ribosomal protein L31
Ae: 60S ribosomal protein L32
Af: 60S ribosomal protein L35a
Ag: 60S ribosomal protein L34
Ah: 60S ribosomal protein L35
Ai: 60S ribosomal protein L36
Aj: 60S ribosomal protein L37
Ak: 60S ribosomal protein L38
Al: 60S ribosomal protein L39
Am: 60S ribosomal protein L40
An: 60S ribosomal protein L41
Ao: 60S ribosomal protein L36a
Ap: 60S ribosomal protein L37a
At: 60S ribosomal protein L28
A2: 28S ribosomal RNA
B1: 18S ribosomal RNA
BD: 40S ribosomal protein S3
BE: 40S ribosomal protein S4, Y isoform 1
BF: 40S ribosomal protein S5
BG: 40S ribosomal protein S6
BH: 40S ribosomal protein S7
BI: 40S ribosomal protein S8
BJ: 40S ribosomal protein S9
BK: 40S ribosomal protein S10
BL: 40S ribosomal protein S11
BM: 40S ribosomal protein S12
BN: 40S ribosomal protein S13
BO: 40S ribosomal protein S14
BP: 40S ribosomal protein S15
BQ: 40S ribosomal protein S16
BR: 40S ribosomal protein S17
BS: 40S ribosomal protein S18
BT: 40S ribosomal protein S19
BU: 40S ribosomal protein S20
BV: 40S ribosomal protein S21
BW: 40S ribosomal protein S15a
BX: 40S ribosomal protein S23
BY: 40S ribosomal protein S24
BZ: 40S ribosomal protein S25
Ba: 40S ribosomal protein S26
Bb: 40S ribosomal protein S27
Bc: 40S ribosomal protein S28
Bd: 40S ribosomal protein S29
Be: 40S ribosomal protein S30
Bf: Ubiquitin-40S ribosomal protein S27a
Bg: Receptor of activated protein C kinase 1
Bv: tRNA
Bx: mRNA
A: Proprotein convertase subtilisin/kexin type 9
hetero molecules


Theoretical massNumber of molelcules
Total (without water)3,168,064414
Polymers3,159,38082
Non-polymers8,684332
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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60S ribosomal protein ... , 42 types, 42 molecules AAABACADAEAFAGAHAIAJALAMANAOAPAQARASATAUAVAWAXAYAZAaAbAcAdAe...

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


Mass: 26998.613 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62917
#3: Protein 60S ribosomal protein L3 / HIV-1 TAR RNA-binding protein B / TARBP-B / Large ribosomal subunit protein uL3


Mass: 45222.949 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P39023
#5: Protein 60S ribosomal protein L4 / 60S ribosomal protein L1 / Large ribosomal subunit protein uL4


Mass: 41171.547 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P36578
#9: Protein 60S ribosomal protein L5 / Large ribosomal subunit protein uL18


Mass: 34091.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46777
#10: Protein 60S ribosomal protein L6 / Large ribosomal subunit protein eL6 / Neoplasm-related protein C140 / Tax-responsive enhancer ...Large ribosomal subunit protein eL6 / Neoplasm-related protein C140 / Tax-responsive enhancer element-binding protein 107 / TaxREB107


Mass: 28378.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q02878
#11: Protein 60S ribosomal protein L7 / Large ribosomal subunit protein uL30


Mass: 27733.146 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P18124
#12: Protein 60S ribosomal protein L7a / Large ribosomal subunit protein eL8 / PLA-X polypeptide / Surfeit locus protein 3


Mass: 26724.568 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62424
#13: Protein 60S ribosomal protein L9 / Large ribosomal subunit protein uL6


Mass: 21770.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P32969
#14: Protein 60S ribosomal protein L10 / Laminin receptor homolog / Large ribosomal subunit protein uL16 / Protein QM / Ribosomal protein ...Laminin receptor homolog / Large ribosomal subunit protein uL16 / Protein QM / Ribosomal protein L10 / Tumor suppressor QM


Mass: 24381.760 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P27635
#15: Protein 60S ribosomal protein L11 / CLL-associated antigen KW-12 / Large ribosomal subunit protein uL5


Mass: 19270.318 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62913
#16: Protein 60S ribosomal protein L13 / Breast basic conserved protein 1 / Large ribosomal subunit protein eL13


Mass: 23574.697 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P26373
#17: Protein 60S ribosomal protein L14 / CAG-ISL 7 / Large ribosomal subunit protein eL14


Mass: 16220.309 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P50914
#18: Protein 60S ribosomal protein L15 / Large ribosomal subunit protein eL15


Mass: 24076.088 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61313
#19: Protein 60S ribosomal protein L13a / 23 kDa highly basic protein / Large ribosomal subunit protein uL13


Mass: 22820.395 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P40429
#20: Protein 60S ribosomal protein L17 / 60S ribosomal protein L23 / Large ribosomal subunit protein uL22 / PD-1


Mass: 17757.627 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P18621
#21: Protein 60S ribosomal protein L18 / Large ribosomal subunit protein eL18


Mass: 21556.482 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q07020
#22: Protein 60S ribosomal protein L19 / Large ribosomal subunit protein eL19


Mass: 21742.146 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P84098
#23: Protein 60S ribosomal protein L18a / Large ribosomal subunit protein eL20


Mass: 20661.340 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q02543
#24: Protein 60S ribosomal protein L21 / Large ribosomal subunit protein eL21


Mass: 18276.518 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46778
#25: Protein 60S ribosomal protein L22 / EBER-associated protein / EAP / Epstein-Barr virus small RNA-associated protein / Heparin-binding ...EBER-associated protein / EAP / Epstein-Barr virus small RNA-associated protein / Heparin-binding protein HBp15 / Large ribosomal subunit protein eL22


Mass: 11481.248 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P35268
#26: Protein 60S ribosomal protein L23


Mass: 13828.295 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9BTQ7, UniProt: P62829*PLUS
#27: Protein 60S ribosomal protein L24 / 60S ribosomal protein L30 / Large ribosomal subunit protein eL24


Mass: 14087.417 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P83731
#28: Protein 60S ribosomal protein L23a / Large ribosomal subunit protein uL23


Mass: 13614.023 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62750
#29: Protein 60S ribosomal protein L26 / Large ribosomal subunit protein uL24


Mass: 15161.899 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61254
#30: Protein 60S ribosomal protein L27 / Large ribosomal subunit protein eL27


Mass: 15647.584 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61353
#31: Protein 60S ribosomal protein L27a / Large ribosomal subunit protein uL15


Mass: 16473.340 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46776
#32: Protein 60S ribosomal protein L29 / Cell surface heparin-binding protein HIP / Large ribosomal subunit protein eL29


Mass: 13582.337 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P47914
#33: Protein 60S ribosomal protein L30 / Large ribosomal subunit protein eL30


Mass: 11500.556 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62888
#34: Protein 60S ribosomal protein L31 / Large ribosomal subunit protein eL31


Mass: 12506.581 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62899
#35: Protein 60S ribosomal protein L32 / Large ribosomal subunit protein eL32


Mass: 15179.215 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62910
#36: Protein 60S ribosomal protein L35a / Cell growth-inhibiting gene 33 protein / Large ribosomal subunit protein eL33


Mass: 12433.548 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P18077
#37: Protein 60S ribosomal protein L34 / Large ribosomal subunit protein eL34


Mass: 12994.621 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P49207
#38: Protein 60S ribosomal protein L35 / Large ribosomal subunit protein uL29


Mass: 14462.429 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P42766
#39: Protein 60S ribosomal protein L36 / Large ribosomal subunit protein eL36


Mass: 11373.708 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9Y3U8
#40: Protein 60S ribosomal protein L37 / G1.16 / Large ribosomal subunit protein eL37


Mass: 9864.596 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61927
#41: Protein 60S ribosomal protein L38 / Large ribosomal subunit protein eL38


Mass: 8107.752 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63173
#42: Protein/peptide 60S ribosomal protein L39 / Large ribosomal subunit protein eL39


Mass: 6295.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62891
#43: Protein/peptide 60S ribosomal protein L40 / CEP52 / Ubiquitin A-52 residue ribosomal protein fusion product 1


Mass: 5957.237 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62987
#44: Protein/peptide 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
#45: Protein 60S ribosomal protein L36a / 60S ribosomal protein L44 / Cell growth-inhibiting gene 15 protein / Cell migration-inducing gene 6 ...60S ribosomal protein L44 / Cell growth-inhibiting gene 15 protein / Cell migration-inducing gene 6 protein / Large ribosomal subunit protein eL42


Mass: 12345.776 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P83881
#46: Protein 60S ribosomal protein L37a / Large ribosomal subunit protein eL43


Mass: 10168.153 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61513
#47: Protein 60S ribosomal protein L28 / Large ribosomal subunit protein eL28


Mass: 13991.366 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46779

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40S ribosomal protein ... , 31 types, 31 molecules BABBBCBDBEBFBGBHBIBJBKBLBMBNBOBPBQBRBSBTBUBVBWBXBYBZBaBbBcBdBe

#2: Protein 40S ribosomal protein SA / 37 kDa laminin receptor precursor / 37LRP / 37/67 kDa laminin receptor / LRP/LR / 67 kDa laminin ...37 kDa laminin receptor precursor / 37LRP / 37/67 kDa laminin receptor / LRP/LR / 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 / Small ribosomal subunit protein uS2


Mass: 24245.740 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P08865
#4: Protein 40S ribosomal protein S3a / Small ribosomal subunit protein eS1 / v-fos transformation effector protein / Fte-1


Mass: 24660.012 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61247
#6: Protein 40S ribosomal protein S2 / 40S ribosomal protein S4 / Protein LLRep3 / Small ribosomal subunit protein uS5


Mass: 24574.971 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P15880
#50: Protein 40S ribosomal protein S3 / Small ribosomal subunit protein uS3


Mass: 24357.590 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P23396
#51: Protein 40S ribosomal protein S4, Y isoform 1 / Small ribosomal subunit protein eS4


Mass: 28893.043 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P22090
#52: Protein 40S ribosomal protein S5 / Small ribosomal subunit protein uS7


Mass: 21424.836 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46782
#53: Protein 40S ribosomal protein S6 / Phosphoprotein NP33 / Small ribosomal subunit protein eS6


Mass: 26913.867 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62753
#54: Protein 40S ribosomal protein S7 / Small ribosomal subunit protein eS7


Mass: 20990.465 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62081
#55: Protein 40S ribosomal protein S8 / Small ribosomal subunit protein eS8


Mass: 24132.191 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62241
#56: Protein 40S ribosomal protein S9 / Small ribosomal subunit protein uS4


Mass: 21222.221 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46781
#57: Protein 40S ribosomal protein S10 / Small ribosomal subunit protein eS10


Mass: 11773.953 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46783
#58: Protein 40S ribosomal protein S11 / Small ribosomal subunit protein uS17


Mass: 17910.176 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62280
#59: Protein 40S ribosomal protein S12 / Small ribosomal subunit protein eS12


Mass: 13393.658 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P25398
#60: Protein 40S ribosomal protein S13 / Small ribosomal subunit protein uS15


Mass: 17057.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62277
#61: Protein 40S ribosomal protein S14 / Small ribosomal subunit protein uS11


Mass: 14544.659 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62263
#62: Protein 40S ribosomal protein S15 / RIG protein / Small ribosomal subunit protein uS19


Mass: 14273.879 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62841
#63: Protein 40S ribosomal protein S16 / Small ribosomal subunit protein uS9


Mass: 15765.480 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62249
#64: Protein 40S ribosomal protein S17 / Small ribosomal subunit protein eS17


Mass: 14447.793 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P08708
#65: Protein 40S ribosomal protein S18 / Ke-3 / Ke3 / Small ribosomal subunit protein uS13


Mass: 16383.064 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62269
#66: Protein 40S ribosomal protein S19 / Small ribosomal subunit protein eS19


Mass: 15822.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P39019
#67: Protein 40S ribosomal protein S20 / Small ribosomal subunit protein uS10


Mass: 11029.072 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P60866
#68: Protein 40S ribosomal protein S21 / Small ribosomal subunit protein eS21


Mass: 8863.111 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63220
#69: Protein 40S ribosomal protein S15a / Small ribosomal subunit protein uS8


Mass: 14734.357 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62244
#70: Protein 40S ribosomal protein S23 / Small ribosomal subunit protein uS12


Mass: 15372.082 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62266
#71: Protein 40S ribosomal protein S24 / Small ribosomal subunit protein eS24


Mass: 14489.176 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62847
#72: Protein 40S ribosomal protein S25 / Small ribosomal subunit protein eS25


Mass: 9801.748 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62851
#73: Protein 40S ribosomal protein S26 / Small ribosomal subunit protein eS26


Mass: 11087.117 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62854
#74: Protein 40S ribosomal protein S27 / Metallopan-stimulin 1 / MPS-1 / Small ribosomal subunit protein eS27


Mass: 9000.570 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P42677
#75: Protein 40S ribosomal protein S28 / Small ribosomal subunit protein eS28


Mass: 7007.069 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62857
#76: Protein 40S ribosomal protein S29 / Small ribosomal subunit protein uS14


Mass: 6121.210 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62273
#77: Protein 40S ribosomal protein S30


Mass: 6239.447 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: E9PR30, UniProt: P62861*PLUS

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RNA chain , 6 types, 6 molecules A3A4A2B1BvBx

#7: RNA chain 5.8S ribosomal RNA


Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
#8: RNA chain 5S ribosomal RNA


Mass: 38385.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
#48: RNA chain 28S ribosomal RNA


Mass: 1180347.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
#49: RNA chain 18S ribosomal RNA


Mass: 551108.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
#80: RNA chain tRNA


Mass: 24485.539 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)
#81: RNA chain mRNA


Mass: 4853.695 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)

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Protein , 2 types, 2 molecules BfBg

#78: Protein Ubiquitin-40S ribosomal protein S27a / Ubiquitin carboxyl extension protein 80


Mass: 8645.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979
#79: 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: 34726.164 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244

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Protein/peptide , 1 types, 1 molecules A

#82: Protein/peptide Proprotein convertase subtilisin/kexin type 9 / Neural apoptosis-regulated convertase 1 / NARC-1 / Proprotein convertase 9 / PC9 / Subtilisin/kexin- ...Neural apoptosis-regulated convertase 1 / NARC-1 / Proprotein convertase 9 / PC9 / Subtilisin/kexin-like protease PC9


Mass: 2886.409 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q8NBP7

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Non-polymers , 3 types, 332 molecules

#83: Chemical...
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 326 / Source method: obtained synthetically / Formula: Mg
#84: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: Zn
#85: Chemical ChemComp-MVM / N-(3-chloropyridin-2-yl)-N-[(3R)-piperidin-3-yl]-4-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)benzamide


Mass: 433.894 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H20ClN7O

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Human ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like molecule with PP tRNA
Type: RIBOSOME / Entity ID: #1-#82 / Source: NATURAL
Source (natural)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: unspecified
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

CTF correctionType: NONE
3D reconstructionResolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 7214 / Symmetry type: POINT

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