7zep
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Human SLFN11 E209A dimer== | |
| + | <StructureSection load='7zep' size='340' side='right'caption='[[7zep]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7zep]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZEP FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zep OCA], [https://pdbe.org/7zep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zep RCSB], [https://www.ebi.ac.uk/pdbsum/7zep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zep ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SLN11_HUMAN SLN11_HUMAN] Inhibitor of DNA replication that promotes cell death in response to DNA damage (PubMed:22927417, PubMed:26658330, PubMed:29395061). Acts as a guardian of the genome by killing cells with defective replication (PubMed:29395061). Persistently blocks stressed replication forks by opening chromatin across replication initiation sites at stressed replication forks, possibly leading to unwind DNA ahead of the MCM helicase and block fork progression, ultimately leading to cell death (PubMed:29395061). Upon DNA damage, inhibits translation of ATR or ATM based on distinct codon usage without disrupting early DNA damage response signaling (PubMed:30374083). Antiviral restriction factor with manganese-dependent type II tRNA endoribonuclease (PubMed:36115853). A single tRNA molecule is bound and cleaved by the SLFN11 dimer (PubMed:36115853). Specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1) by acting as a specific inhibitor of the synthesis of retroviruses encoded proteins in a codon-usage-dependent manner (PubMed:23000900). Impairs the replication of human cytomegalovirus (HCMV) and some Flaviviruses (PubMed:35105802, PubMed:36115853). Exploits the unique viral codon bias towards A/T nucleotides (PubMed:23000900). Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis (PubMed:23000900).<ref>PMID:22927417</ref> <ref>PMID:23000900</ref> <ref>PMID:26658330</ref> <ref>PMID:29395061</ref> <ref>PMID:30374083</ref> <ref>PMID:35105802</ref> <ref>PMID:36115853</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | Mechanistic understanding of human SLFN11.,Metzner FJ, Wenzl SJ, Kugler M, Krebs S, Hopfner KP, Lammens K Nat Commun. 2022 Sep 17;13(1):5464. doi: 10.1038/s41467-022-33123-0. PMID:36115853<ref>PMID:36115853</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7zep" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Kugler M]] | ||
| + | [[Category: Lammens K]] | ||
| + | [[Category: Metzner FJ]] | ||
| + | [[Category: Wenzl SJ]] | ||
Current revision
Human SLFN11 E209A dimer
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