2k3w: Difference between revisions

Latest revision as of 19:09, 29 May 2024

NMR structure of VPS4A-MIT-CHMP6

Structural highlights

2k3w is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 pathway mediates membrane remodeling during enveloped virus budding, cytokinesis, and intralumenal endosomal vesicle formation. Late in the pathway, a subset of membrane-associated ESCRT-III proteins display terminal amphipathic "MIM1" helices that bind and recruit VPS4 ATPases via their MIT domains. We now report that VPS4 MIT domains also bind a second, "MIM2" motif found in a different subset of ESCRT-III subunits. The solution structure of the VPS4 MIT-CHMP6 MIM2 complex revealed that MIM2 elements bind in extended conformations along the groove between the first and third helices of the MIT domain. Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. MIT-MIM2 interactions appear to be common throughout the ESCRT pathway and possibly elsewhere, and we suggest how these interactions could contribute to a mechanism in which VPS4 and ESCRT-III proteins function together to constrict the necks of budding vesicles.

Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding.,Kieffer C, Skalicky JJ, Morita E, De Domenico I, Ward DM, Kaplan J, Sundquist WI Dev Cell. 2008 Jul;15(1):62-73. PMID:18606141^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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:https://dx.doi.org/10.1242/jcs.00998
↑ Kieffer C, Skalicky JJ, Morita E, De Domenico I, Ward DM, Kaplan J, Sundquist WI. Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding. Dev Cell. 2008 Jul;15(1):62-73. PMID:18606141 doi:10.1016/j.devcel.2008.05.014

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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:https://dx.doi.org/10.1242/jcs.00998

[4] Kieffer C, Skalicky JJ, Morita E, De Domenico I, Ward DM, Kaplan J, Sundquist WI. Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding. Dev Cell. 2008 Jul;15(1):62-73. PMID:18606141 doi:10.1016/j.devcel.2008.05.014

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[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 ==NMR structure of VPS4A-MIT-CHMP6==
-<StructureSection load='2k3w' size='340' side='right'caption='[[2k3w]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2k3w' size='340' side='right'caption='[[2k3w]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2k3w]] 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=2K3W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K3W FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2k3w]] 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=2K3W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K3W 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]), CHMP6, VPS20 ([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=2k3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k3w OCA], [https://pdbe.org/2k3w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k3w RCSB], [https://www.ebi.ac.uk/pdbsum/2k3w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k3w ProSAT]</span></td></tr>
 </table>
 == 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/CHMP6_HUMAN CHMP6_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. In the ESCRT-III complex, it probably serves as an acceptor for the ESCRT-II complex on endosomal membranes.
+[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Domini, I De]]
+[[Category: De Domini I]]
-[[Category: Kaplan, J]]
+[[Category: Kaplan J]]
-[[Category: Kieffer, C]]
+[[Category: Kieffer C]]
-[[Category: Morita, E]]
+[[Category: Morita E]]
-[[Category: Skalicky, J J]]
+[[Category: Skalicky JJ]]
-[[Category: Sundquist, W I]]
+[[Category: Sundquist WI]]
-[[Category: Ward, D M]]
+[[Category: Ward DM]]
-[[Category: Atp-binding]]
-[[Category: Chmp6]]
-[[Category: Coiled coil]]
-[[Category: Endosome]]
-[[Category: Esrct-iii]]
-[[Category: Lipoprotein]]
-[[Category: Membrane]]
-[[Category: Mit]]
-[[Category: Myristate]]
-[[Category: Nucleotide-binding]]
-[[Category: Protein transport]]
-[[Category: Transport]]

2k3w: Difference between revisions

Latest revision as of 19:09, 29 May 2024

NMR structure of VPS4A-MIT-CHMP6

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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