Structural highlights
Function
[IST1_YEAST] Involved in a late step in sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles. The lumenal sequestrated membrane proteins are targeted into the vacuole after fusion of the endosome with the vacuole. Regulates the recruitment of VPS4 to the ESCRT-III complex, probably in conjunction with DID2, and VPS4 catalyzes the disassembly of the ESCRT-III complex.[1] [2]
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 machinery functions in several important eukaryotic cellular processes. The AAA-ATPase Vps4 catalyzes disassembly of the ESCRT-III complex and may regulate membrane deformation and vesicle scission as well. Ist1 was proposed to be a regulator of Vps4, but its mechanism of action was unclear. The crystal structure of the N-terminal domain of Ist1 (Ist1NTD) reveals an ESCRT-III subunit-like fold, implicating Ist1 as a divergent ESCRT-III family member. Ist1NTD specifically binds to the ESCRT-III subunit Did2, and cocrystallization of Ist1NTD with a Did2 fragment shows that Ist1 interacts with the Did2 C-terminal MIM1 (MIT-interacting motif 1) via a novel MIM-binding structural motif. This arrangement indicates a mechanism for intermolecular ESCRT-III subunit association and may also suggest one form of ESCRT-III subunit autoinhibition via intramolecular interaction.
Structural basis of Ist1 function and Ist1-Did2 interaction in the multivesicular body pathway and cytokinesis.,Xiao J, Chen XW, Davies BA, Saltiel AR, Katzmann DJ, Xu Z Mol Biol Cell. 2009 Aug;20(15):3514-24. Epub 2009 May 28. PMID:19477918[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dimaano C, Jones CB, Hanono A, Curtiss M, Babst M. Ist1 regulates Vps4 localization and assembly. Mol Biol Cell. 2008 Feb;19(2):465-74. Epub 2007 Nov 21. PMID:18032582 doi:http://dx.doi.org/E07-08-0747
- ↑ Rue SM, Mattei S, Saksena S, Emr SD. Novel Ist1-Did2 complex functions at a late step in multivesicular body sorting. Mol Biol Cell. 2008 Feb;19(2):475-84. Epub 2007 Nov 21. PMID:18032584 doi:http://dx.doi.org/E07-07-0694
- ↑ Xiao J, Chen XW, Davies BA, Saltiel AR, Katzmann DJ, Xu Z. Structural basis of Ist1 function and Ist1-Did2 interaction in the multivesicular body pathway and cytokinesis. Mol Biol Cell. 2009 Aug;20(15):3514-24. Epub 2009 May 28. PMID:19477918 doi:10.1091/mbc.E09-05-0403
