+Open data
-Basic information
Entry | Database: PDB / ID: 7zel | |||||||||
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Title | Human SLFN11 dimer apoenzyme | |||||||||
Components | Schlafen family member 11 | |||||||||
Keywords | HYDROLASE / tRNA endonuclease / single-strand DNA binding protein | |||||||||
Function / homology | Function and homology information replication fork arrest / negative regulation of G1/S transition of mitotic cell cycle / immune system process / negative regulation of DNA replication / site of DNA damage / helicase activity / defense response to virus / endonuclease activity / tRNA binding / Hydrolases; Acting on ester bonds ...replication fork arrest / negative regulation of G1/S transition of mitotic cell cycle / immune system process / negative regulation of DNA replication / site of DNA damage / helicase activity / defense response to virus / endonuclease activity / tRNA binding / Hydrolases; Acting on ester bonds / chromatin remodeling / DNA damage response / ATP hydrolysis activity / DNA binding / nucleoplasm / ATP binding / nucleus / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Metzner, F.J. / Kugler, M. / Wenzl, S.J. / Lammens, K. | |||||||||
Funding support | Germany, European Union, 2items
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Citation | Journal: Nat Commun / Year: 2022 Title: Mechanistic understanding of human SLFN11. Authors: Felix J Metzner / Simon J Wenzl / Michael Kugler / Stefan Krebs / Karl-Peter Hopfner / Katja Lammens / Abstract: Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in response to ...Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in response to replication stress and inhibits replication of certain viruses such as the human immunodeficiency virus 1 (HIV-1) by modulating the tRNA pool. SLFN11 has been identified as a predictive biomarker in cancer, as its expression correlates with a beneficial response to DNA damage inducing anticancer drugs. However, the mechanism and interdependence of these two functions are largely unknown. Here, we present cryo-electron microscopy (cryo-EM) structures of human SLFN11 in its dimeric apoenzyme state, bound to tRNA and in complex with single-strand DNA. Full-length SLFN11 neither hydrolyses nor binds ATP and the helicase domain appears in an autoinhibited state. Together with biochemical and structure guided mutagenesis studies, our data give detailed insights into the mechanism of endoribonuclease activity as well as suggestions on how SLFN11 may block stressed replication forks. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7zel.cif.gz | 304.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7zel.ent.gz | 241.9 KB | Display | PDB format |
PDBx/mmJSON format | 7zel.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7zel_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7zel_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7zel_validation.xml.gz | 57.8 KB | Display | |
Data in CIF | 7zel_validation.cif.gz | 85.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ze/7zel ftp://data.pdbj.org/pub/pdb/validation_reports/ze/7zel | HTTPS FTP |
-Related structure data
Related structure data | 14690MC 7zepC 7zesC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 106207.914 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLFN11 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q7Z7L1, Hydrolases; Acting on acid anhydrides #2: Chemical | #3: Chemical | Has ligand of interest | N | |
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-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: SLFN11 dimer / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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 defocus max: 2900 nm / Nominal defocus min: 1100 nm |
Image recording | Electron dose: 49.65 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 522494 / Symmetry type: POINT |