| Structural highlights
2lxm is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 2lxl |
| Gene: | C6orf55, HSPC228, My012, VTA1 (HUMAN), C9orf83, CGI-34, CHMP5, HSPC177, PNAS-114, PNAS-2, SNF7DC2 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[VTA1_HUMAN] Involved in the endosomal multivesicular bodies (MVB) pathway. 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. Thought to be a cofactor of VPS4A/B, which catalyzes disassembles membrane-associated ESCRT-III assemblies. Involved in the sorting and down-regulation of EGFR (By similarity). Involved in HIV-1 budding.[1] [CHMP5_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 HIV-1 p6- and p9-dependent virus release.[2]
Publication Abstract from PubMed
The ESCRT pathway remodels membranes during multivesicular body biogenesis, the abscission stage of cytokinesis, and enveloped virus budding. The ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes, and the LIP5 protein helps regulate their interactions by binding directly to a subset of ESCRT-III proteins and to VPS4. We have investigated the biochemical and structural basis for different LIP5 ligand interactions and show that the first MIT (Microtubule Interacting and Trafficking) module of the tandem LIP5 MIT domain binds CHMP1B (and other ESCRT-III proteins) through canonical Type 1 MIT Interacting Motif (MIM1) interactions. In contrast, the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein, CHMP5. A solution structure of the relevant LIP5-CHMP5 complex reveals that CHMP5 helices 5 and 6 and adjacent linkers form an amphipathic "Leucine Collar" that wraps almost completely around the second LIP5 MIT module but makes only limited contacts with the first MIT module. LIP5 binds MIM1-containing ESCRT-III proteins, CHMP5 and VPS4 ligands independently in vitro, but these interactions are coupled within cells because formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5. Our studies thus reveal how the tandem MIT domain of LIP5 binds different types of ESCRT-III proteins, promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate.
Interactions of the Human LIP5 Regulatory Protein with Endosomal Sorting Complexes Required for Transport.,Skalicky JJ, Arii J, Wenzel DM, Stubblefield WM, Katsuyama A, Uter NT, Bajorek M, Myszka DG, Sundquist WI J Biol Chem. 2012 Oct 26. PMID:23105106[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ward DM, Vaughn MB, Shiflett SL, White PL, Pollock AL, Hill J, Schnegelberger R, Sundquist WI, Kaplan J. The role of LIP5 and CHMP5 in multivesicular body formation and HIV-1 budding in mammalian cells. J Biol Chem. 2005 Mar 18;280(11):10548-55. Epub 2005 Jan 11. PMID:15644320 doi:http://dx.doi.org/M413734200
- ↑ Martin-Serrano J, Yarovoy A, Perez-Caballero D, Bieniasz PD. Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12414-9. Epub 2003 Sep 30. PMID:14519844 doi:10.1073/pnas.2133846100
- ↑ Skalicky JJ, Arii J, Wenzel DM, Stubblefield WM, Katsuyama A, Uter NT, Bajorek M, Myszka DG, Sundquist WI. Interactions of the Human LIP5 Regulatory Protein with Endosomal Sorting Complexes Required for Transport. J Biol Chem. 2012 Oct 26. PMID:23105106 doi:http://dx.doi.org/10.1074/jbc.M112.417899
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