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| | ==VPS4A MIT-CHMP1A complex== | | ==VPS4A MIT-CHMP1A complex== |
| - | <StructureSection load='2jq9' size='340' side='right'caption='[[2jq9]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2jq9' size='340' side='right'caption='[[2jq9]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jq9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JQ9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jq9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JQ9 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VPS4A, VPS4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PCOLN3, CHMP1, CHMP1A, KIAA0047, PRSM1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2jq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jq9 OCA], [https://pdbe.org/2jq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jq9 RCSB], [https://www.ebi.ac.uk/pdbsum/2jq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jq9 ProSAT]</span></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=2jq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jq9 OCA], [https://pdbe.org/2jq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jq9 RCSB], [https://www.ebi.ac.uk/pdbsum/2jq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jq9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/VPS4A_HUMAN VPS4A_HUMAN]] Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. 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. In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Involved in cytokinesis.<ref>PMID:11563910</ref> <ref>PMID:11595185</ref> <ref>PMID:15075231</ref> [[https://www.uniprot.org/uniprot/CHM1A_HUMAN CHM1A_HUMAN]] Probable peripherally associated 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 cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing.<ref>PMID:8863740</ref> <ref>PMID:11559747</ref> <ref>PMID:11559748</ref> <ref>PMID:19129479</ref> <ref>PMID:23045692</ref>
| + | [https://www.uniprot.org/uniprot/VPS4A_HUMAN VPS4A_HUMAN] Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. 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. In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Involved in cytokinesis.<ref>PMID:11563910</ref> <ref>PMID:11595185</ref> <ref>PMID:15075231</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ghaffarian, S]] | + | [[Category: Ghaffarian S]] |
| - | [[Category: Kieffer, C]] | + | [[Category: Kieffer C]] |
| - | [[Category: Skalicky, J J]] | + | [[Category: Skalicky JJ]] |
| - | [[Category: Stuchell-Brereton, M D]] | + | [[Category: Stuchell-Brereton MD]] |
| - | [[Category: Sundquist, W I]] | + | [[Category: Sundquist WI]] |
| - | [[Category: Chmp1a]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Four helix bundle]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Vps4a mit]]
| + | |
| Structural highlights
Function
VPS4A_HUMAN Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. 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. In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Involved in cytokinesis.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The ESCRT (endosomal sorting complex required for transport) pathway is required for terminal membrane fission events in several important biological processes, including endosomal intraluminal vesicle formation, HIV budding and cytokinesis. VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly, possibly in conjunction with membrane fission. Here we show that the microtubule interacting and transport (MIT) domains of human VPS4A and VPS4B bind conserved sequence motifs located at the carboxy termini of the CHMP1-3 class of ESCRT-III proteins. Structures of VPS4A MIT-CHMP1A and VPS4B MIT-CHMP2B complexes reveal that the C-terminal CHMP motif forms an amphipathic helix that binds in a groove between the last two helices of the tetratricopeptide-like repeat (TPR) of the VPS4 MIT domain, but in the opposite orientation to that of a canonical TPR interaction. Distinct pockets in the MIT domain bind three conserved leucine residues of the CHMP motif, and mutations that inhibit these interactions block VPS4 recruitment, impair endosomal protein sorting and relieve dominant-negative VPS4 inhibition of HIV budding. Thus, our studies reveal how the VPS4 ATPases recognize their CHMP substrates to facilitate the membrane fission events required for the release of viruses, endosomal vesicles and daughter cells.
ESCRT-III recognition by VPS4 ATPases.,Stuchell-Brereton MD, Skalicky JJ, Kieffer C, Karren MA, Ghaffarian S, Sundquist WI Nature. 2007 Oct 11;449(7163):740-4. PMID:17928862[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Scheuring S, Rohricht RA, Schoning-Burkhardt B, Beyer A, Muller S, Abts HF, Kohrer K. Mammalian cells express two VPS4 proteins both of which are involved in intracellular protein trafficking. J Mol Biol. 2001 Sep 21;312(3):469-80. PMID:11563910 doi:10.1006/jmbi.2001.4917
- ↑ Garrus JE, von Schwedler UK, Pornillos OW, Morham SG, Zavitz KH, Wang HE, Wettstein DA, Stray KM, Cote M, Rich RL, Myszka DG, Sundquist WI. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell. 2001 Oct 5;107(1):55-65. PMID:11595185
- ↑ Sachse M, Strous GJ, Klumperman J. ATPase-deficient hVPS4 impairs formation of internal endosomal vesicles and stabilizes bilayered clathrin coats on endosomal vacuoles. J Cell Sci. 2004 Apr 1;117(Pt 9):1699-708. Epub 2004 Mar 9. PMID:15075231 doi:http://dx.doi.org/10.1242/jcs.00998
- ↑ Stuchell-Brereton MD, Skalicky JJ, Kieffer C, Karren MA, Ghaffarian S, Sundquist WI. ESCRT-III recognition by VPS4 ATPases. Nature. 2007 Oct 11;449(7163):740-4. PMID:17928862 doi:http://dx.doi.org/10.1038/nature06172
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