5aja
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5aja is ON HOLD until Paper Publication Authors: Schwefel, D., Boucherit, V.C., Christodoulou, E., Walker, P.A., Stoye, J.P., Bishop, K.N., Taylor, ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of mandrill SAMHD1 (amino acid residues 1-114) bound to Vpx isolated from mandrill and human DCAF1 (amino acid residues 1058-1396)== | |
| + | <StructureSection load='5aja' size='340' side='right'caption='[[5aja]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5aja]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mandrillus_sphinx Mandrillus sphinx] and [https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus Simian immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AJA FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.649Å</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=5aja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aja OCA], [https://pdbe.org/5aja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5aja RCSB], [https://www.ebi.ac.uk/pdbsum/5aja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5aja ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DCAF1_HUMAN DCAF1_HUMAN] Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2. Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination. Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (PubMed:23362280). Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription. H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (PubMed:20644714).<ref>PMID:16964240</ref> <ref>PMID:17609381</ref> <ref>PMID:17630831</ref> <ref>PMID:18332868</ref> <ref>PMID:18524771</ref> <ref>PMID:18606781</ref> <ref>PMID:19287380</ref> <ref>PMID:20644714</ref> <ref>PMID:22184063</ref> <ref>PMID:23063525</ref> <ref>PMID:23362280</ref> <ref>PMID:24140421</ref> (Microbial infection) In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT.<ref>PMID:17314515</ref> <ref>PMID:17559673</ref> <ref>PMID:17609381</ref> <ref>PMID:17620334</ref> <ref>PMID:17626091</ref> <ref>PMID:17630831</ref> <ref>PMID:18524771</ref> <ref>PMID:24116224</ref> (Microbial infection) In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage.<ref>PMID:17314515</ref> <ref>PMID:18464893</ref> <ref>PMID:19264781</ref> <ref>PMID:19923175</ref> <ref>PMID:24336198</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of myeloid and resting T cells by depleting dNTPs. To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineages of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation. We present the ternary complex of Vpx from SIV that infects mandrills (SIVmnd-2) with the cullin-4 substrate receptor, DCAF1, and N-terminal and SAM domains from mandrill SAMHD1. The structure reveals details of Vpx lineage-specific targeting of SAMHD1 N-terminal "degron" sequences. Comparison with Vpx from SIV that infects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing Vpx lineages to N- or C-terminal SAMHD1 sequences. Inspection of the Vpx-DCAF1 interface also reveals conservation of Vpx with the evolutionally related HIV-1/SIV accessory protein Vpr. These data suggest a unified model for how Vpx and Vpr exploit DCAF1 to promote viral replication. | ||
| - | + | Molecular Determinants for Recognition of Divergent SAMHD1 Proteins by the Lentiviral Accessory Protein Vpx.,Schwefel D, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IA Cell Host Microbe. 2015 Apr 8;17(4):489-99. doi: 10.1016/j.chom.2015.03.004. PMID:25856754<ref>PMID:25856754</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5aja" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: Schwefel | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| - | [[Category: Stoye | + | *[[VprBP|VprBP]] |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mandrillus sphinx]] | ||
| + | [[Category: Simian immunodeficiency virus]] | ||
| + | [[Category: Bishop KN]] | ||
| + | [[Category: Boucherit VC]] | ||
| + | [[Category: Christodoulou E]] | ||
| + | [[Category: Schwefel D]] | ||
| + | [[Category: Stoye JP]] | ||
| + | [[Category: Taylor IA]] | ||
| + | [[Category: Walker PA]] | ||
Current revision
Crystal structure of mandrill SAMHD1 (amino acid residues 1-114) bound to Vpx isolated from mandrill and human DCAF1 (amino acid residues 1058-1396)
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