Document Detail


Assembly of the AAA ATPase Vps4 on ESCRT-III.
MedLine Citation:
PMID:  20110351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vps4 is a key enzyme that functions in endosomal protein trafficking, cytokinesis, and retroviral budding. Vps4 activity is regulated by its recruitment from the cytoplasm to ESCRT-III, where the protein oligomerizes into an active ATPase. The recruitment and oligomerization steps are mediated by a complex network of at least 12 distinct interactions between Vps4, ESCRT-III, Ist1, Vta1, and Did2. The order of events leading to active, ESCRT-III-associated Vps4 is poorly understood. In this study we present a systematic in vivo analysis of the Vps4 interaction network. The data demonstrated a high degree of redundancy in the network. Although no single interaction was found to be essential for the localization or activity of Vps4, certain interactions proved more important than others. The most significant among these were the binding of Vps4 to Vta1 and to the ESCRT-III subunits Vps2 and Snf7. In our model we propose the formation of a recruitment complex in the cytoplasm that is composed of Did2-Ist1-Vps4, which upon binding to ESCRT-III recruits Vta1. Vta1 in turn is predicted to cause a rearrangement of the Vps4 interactions that initiates the assembly of the active Vps4 oligomer.
Authors:
Anna Shestakova; Abraham Hanono; Stacey Drosner; Matt Curtiss; Brian A Davies; David J Katzmann; Markus Babst
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-28
Journal Detail:
Title:  Molecular biology of the cell     Volume:  21     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-12     Completed Date:  2010-09-08     Revised Date:  2012-04-16    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1059-71     Citation Subset:  IM    
Affiliation:
Department of Biology, University of Utah, Salt Lake City, UT 84112-9202, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphatases / genetics,  metabolism*
Amino Acid Sequence
Endosomal Sorting Complexes Required for Transport / genetics,  metabolism*
Molecular Sequence Data
Protein Structure, Tertiary
Protein Subunits / genetics,  metabolism
Recombinant Fusion Proteins / genetics,  metabolism
Saccharomyces cerevisiae / cytology,  metabolism
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Sequence Alignment
Vesicular Transport Proteins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
R01 GM073024/GM/NIGMS NIH HHS; R01 GM073024-07/GM/NIGMS NIH HHS; R01 GM073024-08/GM/NIGMS NIH HHS; R01 GM074171/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Endosomal Sorting Complexes Required for Transport; 0/Ist1 protein, S cerevisiae; 0/Protein Subunits; 0/Recombinant Fusion Proteins; 0/Saccharomyces cerevisiae Proteins; 0/VPS4 protein, S cerevisiae; 0/VTA1 protein, S cerevisiae; 0/Vesicular Transport Proteins; 0/Vps46 protein, S cerevisiae; EC 3.6.1.-/Adenosine Triphosphatases
Comments/Corrections

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