+Open data
-Basic information
Entry | Database: PDB / ID: 6qkl | ||||||||||||
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Title | Mechanism of eIF6 release from the nascent 60S ribosomal subunit | ||||||||||||
Components |
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Keywords | RIBOSOME / 60S subunit / eIF6 / SBDS / uL16 | ||||||||||||
Function / homology | Function and homology information Recognition of DNA damage by PCNA-containing replication complex / Downregulation of ERBB2:ERBB3 signaling / L13a-mediated translational silencing of Ceruloplasmin expression / APC/C:Cdc20 mediated degradation of Cyclin B / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC-Cdc20 mediated degradation of Nek2A / SRP-dependent cotranslational protein targeting to membrane ...Recognition of DNA damage by PCNA-containing replication complex / Downregulation of ERBB2:ERBB3 signaling / L13a-mediated translational silencing of Ceruloplasmin expression / APC/C:Cdc20 mediated degradation of Cyclin B / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC-Cdc20 mediated degradation of Nek2A / SRP-dependent cotranslational protein targeting to membrane / Separation of Sister Chromatids / Senescence-Associated Secretory Phenotype (SASP) / Autodegradation of the E3 ubiquitin ligase COP1 / ABC-family proteins mediated transport / AUF1 (hnRNP D0) binds and destabilizes mRNA / Degradation of DVL / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Hedgehog ligand biogenesis / Hedgehog 'on' state / Translesion synthesis by POLK / Regulation of RAS by GAPs / MAPK6/MAPK4 signaling / UCH proteinases / Josephin domain DUBs / Ub-specific processing proteases / Metalloprotease DUBs / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Gap-filling DNA repair synthesis and ligation in GG-NER / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / CDK-mediated phosphorylation and removal of Cdc6 / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Formation of a pool of free 40S subunits / GTP hydrolysis and joining of the 60S ribosomal subunit / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / E3 ubiquitin ligases ubiquitinate target proteins / Regulation of PTEN localization / Regulation of PTEN stability and activity / ER Quality Control Compartment (ERQC) / Interleukin-1 signaling / Peroxisomal protein import / Endosomal Sorting Complex Required For Transport (ESCRT) / Negative regulators of DDX58/IFIH1 signaling / Pexophagy / KEAP1-NFE2L2 pathway / Regulation of NF-kappa B signaling / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Regulation of pyruvate metabolism / Orc1 removal from chromatin / Cyclin D associated events in G1 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Neddylation / Iron uptake and transport / Antigen processing: Ubiquitination & Proteasome degradation / Aggrephagy / Regulation of necroptotic cell death / leukocyte chemotaxis / bone marrow development / inner cell mass cell proliferation / maturation of 5.8S rRNA / bone mineralization / ribosomal large subunit binding / preribosome, large subunit precursor / hematopoietic progenitor cell differentiation / phagocytic vesicle / ribosomal subunit export from nucleus / maturation of LSU-rRNA / translation initiation factor activity / extracellular matrix / lipid droplet / mitotic spindle organization / ribosomal large subunit biogenesis / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / spindle pole / modification-dependent protein catabolic process / rRNA processing / protein tag activity / ribosome binding / ribosomal large subunit assembly / large ribosomal subunit rRNA binding / microtubule binding / cytoplasmic translation / cytosolic large ribosomal subunit / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / ubiquitin protein ligase binding / nucleolus / RNA binding / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) Dictyostelium discoideum (eukaryote) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
Authors | Kargas, V. / Warren, A.J. | ||||||||||||
Funding support | United Kingdom, 3items
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Citation | Journal: Nat Struct Mol Biol / Year: 2015 Title: Mechanism of eIF6 release from the nascent 60S ribosomal subunit. Authors: Félix Weis / Emmanuel Giudice / Mark Churcher / Li Jin / Christine Hilcenko / Chi C Wong / David Traynor / Robert R Kay / Alan J Warren / Abstract: SBDS protein (deficient in the inherited leukemia-predisposition disorder Shwachman-Diamond syndrome) and the GTPase EFL1 (an EF-G homolog) activate nascent 60S ribosomal subunits for translation by ...SBDS protein (deficient in the inherited leukemia-predisposition disorder Shwachman-Diamond syndrome) and the GTPase EFL1 (an EF-G homolog) activate nascent 60S ribosomal subunits for translation by catalyzing eviction of the antiassociation factor eIF6 from nascent 60S ribosomal subunits. However, the mechanism is completely unknown. Here, we present cryo-EM structures of human SBDS and SBDS-EFL1 bound to Dictyostelium discoideum 60S ribosomal subunits with and without endogenous eIF6. SBDS assesses the integrity of the peptidyl (P) site, bridging uL16 (mutated in T-cell acute lymphoblastic leukemia) with uL11 at the P-stalk base and the sarcin-ricin loop. Upon EFL1 binding, SBDS is repositioned around helix 69, thus facilitating a conformational switch in EFL1 that displaces eIF6 by competing for an overlapping binding site on the 60S ribosomal subunit. Our data reveal the conserved mechanism of eIF6 release, which is corrupted in both inherited and sporadic leukemias. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6qkl.cif.gz | 924.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6qkl.ent.gz | 703.1 KB | Display | PDB format |
PDBx/mmJSON format | 6qkl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6qkl_validation.pdf.gz | 863.2 KB | Display | wwPDB validaton report |
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Full document | 6qkl_full_validation.pdf.gz | 939.4 KB | Display | |
Data in XML | 6qkl_validation.xml.gz | 75.2 KB | Display | |
Data in CIF | 6qkl_validation.cif.gz | 124.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qk/6qkl ftp://data.pdbj.org/pub/pdb/validation_reports/qk/6qkl | HTTPS FTP |
-Related structure data
Related structure data | 3145MC 3146C 3147C 5an9C 5anbC 5ancC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 1 types, 1 molecules N
#1: RNA chain | Mass: 1205997.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) |
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-60S ribosomal protein ... , 6 types, 6 molecules ABEFGD
#2: Protein | Mass: 45158.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: P34113 |
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#3: Protein | Mass: 21250.656 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: Q54XI5 |
#4: Protein | Mass: 14567.147 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: Q54G86 |
#5: Protein | Mass: 24591.754 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: Q54J69 |
#6: Protein | Mass: 8334.771 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: Q54VN6 |
#11: Protein | Mass: 17811.031 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: Q54J50 |
-Protein , 4 types, 4 molecules HIJC
#7: Protein | Mass: 6170.682 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: P14794 |
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#8: Protein | Mass: 24107.266 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: Q551M2 |
#9: Protein | Mass: 28813.602 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SBDS, CGI-97 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9Y3A5 |
#10: Protein | Mass: 22434.189 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Dictyostelium discoideum (eukaryote) / References: UniProt: P22685 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: DICTYOSTELIUM 60S CARRYING ENDOGENOUS EIF6 WITH RECOMBINANT HUMAN SBDS Type: RIBOSOME / Entity ID: all / Source: MULTIPLE SOURCES |
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Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 120 K / Details: 1 BLOT 6.5S |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 59000 X / Nominal defocus max: 2800 nm / Nominal defocus min: 2200 nm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 43063 / Symmetry type: POINT |