title: Structural basis of molecular recognition between ESCRT-III-like protein Vps60 and AAA-ATPase regulator Vta1 in the multivesicular body pathway.
abstract: The AAA-ATPase Vps4 is critical for function of the multivesicular body sorting pathway, which impacts cellular phenomena ranging from receptor down-regulation to viral budding to cytokinesis. Vps4 activity is stimulated by the interaction between Vta1 and Vps60, but the structural basis for this interaction is unclear. The fragment Vps60(128-186) was reported to display the full activity of Vps60. Vta1 interacts with Vps60 using its N-terminal domain (Vta1NTD). In this work, the structure of Vps60(128-186) in complex with Vta1NTD was determined using NMR techniques, demonstrating a novel recognition mode of the microtubule-interacting and transport (MIT) domain in which Vps60(128-186) interacts with Vta1NTD through helices α4' and α5', extending over Vta1NTD MIT2 domain helices 1-3. The Vps60 binding does not result in Vta1 conformational changes, further revealing the fact that Vps4 ATPase is enhanced by the interaction between Vta1 and Vps60 in an unanticipated manner.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Zhongzheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Cody
authors.initials: C
authors.lastname: Vild
authors.forename: Jiaying
authors.initials: J
authors.lastname: Ju
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Wenxian
authors.initials: W
authors.lastname: Lan
authors.forename: Fuchun
authors.initials: F
authors.lastname: Gong
authors.forename: Maili
authors.initials: M
authors.lastname: Liu
authors.forename: Chunyang
authors.initials: C
authors.lastname: Cao
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D057146:Multivesicular Bodies / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C107528:VPS4 protein, S cerevisiae; C430215:VPS60 protein, S cerevisiae; C487285:VTA1 protein, S cerevisiae; D000251:Adenosine Triphosphatases