6vme

From Proteopedia

Human ESCRT-I heterotetramer headpiece

Structural highlights

6vme is a 24 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.19Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TS101_HUMAN Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The ESCRT complexes drive membrane scission in HIV-1 release, autophagosome closure, multivesicular body biogenesis, cytokinesis, and other cell processes. ESCRT-I is the most upstream complex and bridges the system to HIV-1 Gag in virus release. The crystal structure of the headpiece of human ESCRT-I comprising TSG101-VPS28-VPS37B-MVB12A was determined, revealing an ESCRT-I helical assembly with a 12-molecule repeat. Electron microscopy confirmed that ESCRT-I subcomplexes form helical filaments in solution. Mutation of VPS28 helical interface residues blocks filament formation in vitro and autophagosome closure and HIV-1 release in human cells. Coarse-grained (CG) simulations of ESCRT assembly at HIV-1 budding sites suggest that formation of a 12-membered ring of ESCRT-I molecules is a geometry-dependent checkpoint during late stages of Gag assembly and HIV-1 budding and templates ESCRT-III assembly for membrane scission. These data show that ESCRT-I is not merely a bridging adaptor; it has an essential scaffolding and mechanical role in its own right.

A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.,Flower TG, Takahashi Y, Hudait A, Rose K, Tjahjono N, Pak AJ, Yokom AL, Liang X, Wang HG, Bouamr F, Voth GA, Hurley JH Nat Struct Mol Biol. 2020 May 18. pii: 10.1038/s41594-020-0426-4. doi:, 10.1038/s41594-020-0426-4. PMID:32424346^[4]

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

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Citations

reviews cite this structure

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References

↑ Bishop N, Horman A, Woodman P. Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol. 2002 Apr 1;157(1):91-101. Epub 2002 Mar 26. PMID:11916981 doi:10.1083/jcb.200112080
↑ Morita E, Sandrin V, Chung HY, Morham SG, Gygi SP, Rodesch CK, Sundquist WI. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J. 2007 Oct 3;26(19):4215-27. Epub 2007 Sep 13. PMID:17853893 doi:10.1038/sj.emboj.7601850
↑ Carlton JG, Martin-Serrano J. Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science. 2007 Jun 29;316(5833):1908-12. Epub 2007 Jun 7. PMID:17556548 doi:10.1126/science.1143422
↑ Flower TG, Takahashi Y, Hudait A, Rose K, Tjahjono N, Pak AJ, Yokom AL, Liang X, Wang HG, Bouamr F, Voth GA, Hurley JH. A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission. Nat Struct Mol Biol. 2020 May 18. pii: 10.1038/s41594-020-0426-4. doi:, 10.1038/s41594-020-0426-4. PMID:32424346 doi:http://dx.doi.org/10.1038/s41594-020-0426-4