| Structural highlights
4u7y is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 4u7e, 4u7i |
| Gene: | VPS4B, SKD1, VPS42, MIG1 (HUMAN), IST1, KIAA0174 (HUMAN) |
| Activity: | Vesicle-fusing ATPase, with EC number 3.6.4.6 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[VPS4B_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).[1] [2] [3] [IST1_HUMAN] Proposed to be involved in specific functions of the ESCRT machinery. Is required for efficient abscission during cytokinesis, but not for HIV-1 budding. The involvement in the MVB pathway is not established. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells.[4] [5]
Publication Abstract from PubMed
The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multi-vesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the Microtubule Interacting and Trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-Interacting Motif (MIM). Here, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5 and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. These observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode.
Distinct Mechanisms of Recognizing Endosomal Sorting Complex Required for Transport (ESCRT)-III Protein IST1 by Different Microtubule Interacting and Trafficking (MIT) Domains.,Guo EZ, Xu Z J Biol Chem. 2015 Feb 5. pii: jbc.M114.607903. PMID:25657007[6]
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
- ↑ von Schwedler UK, Stuchell M, Muller B, Ward DM, Chung HY, Morita E, Wang HE, Davis T, He GP, Cimbora DM, Scott A, Krausslich HG, Kaplan J, Morham SG, Sundquist WI. The protein network of HIV budding. Cell. 2003 Sep 19;114(6):701-13. PMID:14505570
- ↑ Lata S, Schoehn G, Jain A, Pires R, Piehler J, Gottlinger HG, Weissenhorn W. Helical structures of ESCRT-III are disassembled by VPS4. Science. 2008 Sep 5;321(5894):1354-7. doi: 10.1126/science.1161070. Epub 2008 Aug, 7. PMID:18687924 doi:10.1126/science.1161070
- ↑ Bajorek M, Morita E, Skalicky JJ, Morham SG, Babst M, Sundquist WI. Biochemical analyses of human IST1 and its function in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1360-73. doi: 10.1091/mbc.E08-05-0475. Epub 2009, Jan 7. PMID:19129479 doi:http://dx.doi.org/10.1091/mbc.E08-05-0475
- ↑ Agromayor M, Carlton JG, Phelan JP, Matthews DR, Carlin LM, Ameer-Beg S, Bowers K, Martin-Serrano J. Essential role of hIST1 in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1374-87. doi: 10.1091/mbc.E08-05-0474. Epub 2009, Jan 7. PMID:19129480 doi:http://dx.doi.org/10.1091/mbc.E08-05-0474
- ↑ Guo EZ, Xu Z. Distinct Mechanisms of Recognizing Endosomal Sorting Complex Required for Transport (ESCRT)-III Protein IST1 by Different Microtubule Interacting and Trafficking (MIT) Domains. J Biol Chem. 2015 Feb 5. pii: jbc.M114.607903. PMID:25657007 doi:http://dx.doi.org/10.1074/jbc.M114.607903
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