Structural highlights
Function
[DID4_YEAST] Required for the sorting and concentration of proteins resulting in the entry of these proteins into the invaginating vesicles of the multivesicular body (MVB). Acts a component of the ESCRT-III complex, which appears to be critical for late steps in MVB sorting, such as membrane invagination and final cargo sorting and recruitment of late-acting components of the sorting machinery. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complex assemblies. Can directly stimulate VPS4 ATPase activity. The DID4/VPS2-VPS24 subcomplex is required for the VPS4-dependent dissociation of ESCRT-III.[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 AAA+ ATPases are essential for various activities such as membrane trafficking, organelle biogenesis, DNA replication, intracellular locomotion, cytoskeletal remodelling, protein folding and proteolysis. The AAA ATPase Vps4, which is central to endosomal traffic to lysosomes, retroviral budding and cytokinesis, dissociates ESCRT complexes (the endosomal sorting complexes required for transport) from membranes. Here we show that, of the six ESCRT--related subunits in yeast, only Vps2 and Did2 bind the MIT (microtubule interacting and transport) domain of Vps4, and that the carboxy-terminal 30 residues of the subunits are both necessary and sufficient for interaction. We determined the crystal structure of the Vps2 C terminus in a complex with the Vps4 MIT domain, explaining the basis for selective ESCRT-III recognition. MIT helices alpha2 and alpha3 recognize a (D/E)xxLxxRLxxL(K/R) motif, and mutations within this motif cause sorting defects in yeast. Our crystal structure of the amino-terminal domain of an archaeal AAA ATPase of unknown function shows that it is closely related to the MIT domain of Vps4. The archaeal ATPase interacts with an archaeal ESCRT-III-like protein even though these organisms have no endomembrane system, suggesting that the Vps4/ESCRT-III partnership is a relic of a function that pre-dates the divergence of eukaryotes and Archaea.
Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4.,Obita T, Saksena S, Ghazi-Tabatabai S, Gill DJ, Perisic O, Emr SD, Williams RL Nature. 2007 Oct 11;449(7163):735-9. PMID:17928861[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Howard TL, Stauffer DR, Degnin CR, Hollenberg SM. CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins. J Cell Sci. 2001 Jul;114(Pt 13):2395-404. PMID:11559748
- ↑ Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD. Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell. 2002 Aug;3(2):271-82. PMID:12194857
- ↑ Azmi IF, Davies BA, Xiao J, Babst M, Xu Z, Katzmann DJ. ESCRT-III family members stimulate Vps4 ATPase activity directly or via Vta1. Dev Cell. 2008 Jan;14(1):50-61. PMID:18194652 doi:http://dx.doi.org/S1534-5807(07)00432-7
- ↑ Obita T, Saksena S, Ghazi-Tabatabai S, Gill DJ, Perisic O, Emr SD, Williams RL. Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4. Nature. 2007 Oct 11;449(7163):735-9. PMID:17928861 doi:10.1038/nature06171
