5h7p
From Proteopedia
NMR structure of the Vta1NTD-Did2(176-204) complex
Structural highlights
Function[VTA1_YEAST] Has a role in the formation of the multivesicular body (MVB). Required for the sorting of lipids to form intralumenal vesicles and for fluid-phase transport to the vacuole. Required for sorting the plasma membrane proteins STE2 and STE3 into the MVB. Acts a cofactor of VSP4, promotes the oligomerization of VPS4 and stimulates its ATPase activity by 6- to 8-fold.[1] [2] [3] [4] [DID2_YEAST] Class E VPS protein implicated in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles. The lumenal sequestrated membrane proteins will be targeted into the vacuole after fusion of the endosome with the vacuole. Probably acts as a peripherally associated 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 recruits late-acting components of the sorting machinery. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complex assemblies. Regulates the membrane association of VPS4. Can stimulate VPS4 ATPase activity directly or via VTA1.[5] [6] [7] [8] [9] [10] [11] Publication Abstract from PubMedAs an AAA-ATPase, Vps4 is important for function of multivesicular bodies (MVB) sorting pathway, which involves in cellular phenomena ranging from receptor down-regulation to viral budding to cytokinesis. The activity of Vps4 is stimulated by the interactions between Vta1 N-terminus (named as Vta1NTD) and Did2 fragment (176-204 aa) (termed as Did2176-204) or Vps60 (128-186 aa) (termed as Vps60128-186). The structural basis of how Vta1NTD binds to Did2176-204 is still unclear. To address this, in this report, the structure of Did2176-204 in complex with Vta1NTD was determined by NMR techniques, demonstrating that Did2176-204 interacts with Vta1NTD through its helix alpha6' extending over the 2nd and the 3rd alpha-helices of Vta1NTD microtubule interacting and transport 1 (MIT1) domain. The residues within Did2176-204 helix alpha6' in the interface make up of an amino acid sequence as E192'xxL195'xxR198'L199'xxL202'R203', identical to type 1 MIT-interacting motif (MIM1) (D/E)xxLxxRLxxL(K/R) of CHMP1A180-196 observed in Vps4-CHMP1A complex structure, indicating that Did2 binds to Vta1NTD through canonical MIM1 interactions. Moreover, the Did2 binding does not result in Vta1NTD significant conformational changes, revealing that Did2, similar to Vps60, enhances Vta1 stimulation of Vps4 ATPase activity in an indirect manner. NMR studies on the interactions between yeast Vta1 and Did2 during the multivesicular bodies sorting pathway.,Shen J, Yang Z, Wang J, Zhao B, Lan W, Wang C, Zhang X, Wild CJ, Liu M, Xu Z, Cao C Sci Rep. 2016 Dec 7;6:38710. doi: 10.1038/srep38710. PMID:27924850[12] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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