5v3r
From Proteopedia
(Difference between revisions)
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<StructureSection load='5v3r' size='340' side='right' caption='[[5v3r]], [[Resolution|resolution]] 1.91Å' scene=''> | <StructureSection load='5v3r' size='340' side='right' caption='[[5v3r]], [[Resolution|resolution]] 1.91Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5v3r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V3R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V3R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v3r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V3R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V3R FirstGlance]. <br> |
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3c3r|3c3r]], [[5v3k|5v3k]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3c3r|3c3r]], [[5v3k|5v3k]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD6IP, AIP1, ALIX, KIAA1375 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5v3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v3r OCA], [http://pdbe.org/5v3r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v3r RCSB], [http://www.ebi.ac.uk/pdbsum/5v3r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v3r ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5v3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v3r OCA], [http://pdbe.org/5v3r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v3r RCSB], [http://www.ebi.ac.uk/pdbsum/5v3r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v3r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PDC6I_HUMAN PDC6I_HUMAN]] Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Appears to be an adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function implies the interaction with CHMP4B. May play a role in the regulation of both apoptosis and cell proliferation.<ref>PMID:14505569</ref> <ref>PMID:14505570</ref> <ref>PMID:14739459</ref> <ref>PMID:17853893</ref> <ref>PMID:17428861</ref> <ref>PMID:17556548</ref> [[http://www.uniprot.org/uniprot/CHM4C_HUMAN CHM4C_HUMAN]] Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-1 p6- and p9-dependent virus release.<ref>PMID:14505569</ref> <ref>PMID:14505570</ref> <ref>PMID:14519844</ref> | [[http://www.uniprot.org/uniprot/PDC6I_HUMAN PDC6I_HUMAN]] Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Appears to be an adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function implies the interaction with CHMP4B. May play a role in the regulation of both apoptosis and cell proliferation.<ref>PMID:14505569</ref> <ref>PMID:14505570</ref> <ref>PMID:14739459</ref> <ref>PMID:17853893</ref> <ref>PMID:17428861</ref> <ref>PMID:17556548</ref> [[http://www.uniprot.org/uniprot/CHM4C_HUMAN CHM4C_HUMAN]] Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-1 p6- and p9-dependent virus release.<ref>PMID:14505569</ref> <ref>PMID:14505570</ref> <ref>PMID:14519844</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cytokinetic abscission facilitates the irreversible separation of daughter cells. This process requires the endosomal-sorting complexes required for transport (ESCRT) machinery and is tightly regulated by charged multivesicular body protein 4C (CHMP4C), an ESCRT-III subunit that engages the abscission checkpoint (NoCut) in response to mitotic problems such as persisting chromatin bridges within the midbody. Importantly, a human polymorphism in CHMP4C (rs35094336, CHMP4C(T232)) increases cancer susceptibility. Here, we explain the structural and functional basis for this cancer association: The CHMP4C(T232) allele unwinds the C-terminal helix of CHMP4C, impairs binding to the early-acting ESCRT factor ALIX, and disrupts the abscission checkpoint. Cells expressing CHMP4C(T232) exhibit increased levels of DNA damage and are sensitized to several conditions that increase chromosome missegregation, including DNA replication stress, inhibition of the mitotic checkpoint, and loss of p53. Our data demonstrate the biological importance of the abscission checkpoint and suggest that dysregulation of abscission by CHMP4C(T232) may synergize with oncogene-induced mitotic stress to promote genomic instability and tumorigenesis. | ||
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| + | A cancer-associated polymorphism in ESCRT-III disrupts the abscission checkpoint and promotes genome instability.,Sadler JBA, Wenzel DM, Williams LK, Guindo-Martinez M, Alam SL, Mercader JM, Torrents D, Ullman KS, Sundquist WI, Martin-Serrano J Proc Natl Acad Sci U S A. 2018 Sep 4. pii: 1805504115. doi:, 10.1073/pnas.1805504115. PMID:30181294<ref>PMID:30181294</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5v3r" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Alam, S L]] | [[Category: Alam, S L]] | ||
[[Category: Sundquist, W I]] | [[Category: Sundquist, W I]] | ||
Revision as of 20:08, 19 September 2018
CHMP4C in complex with ALIX BRO1
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