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PMID: 17543868 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

The Vps27/Hse1 complex is a GAT domain-based scaffold for ubiquitin-dependent sorting.

Developmental cell ·Vol. 12 ·No. 6 ·2007-06-00 ·Pages 973-86

Prag G, Watson H, Kim YC, Beach BM, Ghirlando R, Hummer G, Bonifacino JS, Hurley JH

Abstract

The yeast Vps27/Hse1 complex and the homologous mammalian Hrs/STAM complex deliver ubiquitinated transmembrane proteins to the ESCRT endosomal-sorting pathway. The Vps27/Hse1 complex directly binds to ubiquitinated transmembrane proteins and recruits both ubiquitin ligases and deubiquitinating enzymes. We have solved the crystal structure of the core responsible for the assembly of the Vps27/Hse1 complex at 3.0 A resolution. The structure consists of two intertwined GAT domains, each consisting of two helices from one subunit and one from the other. The two GAT domains are connected by an antiparallel coiled coil, forming a 90 A-long barbell-like structure. This structure places the domains of Vps27 and Hse1 that recruit ubiquitinated cargo and deubiquitinating enzymes close to each other. Coarse-grained Monte Carlo simulations of the Vps27/Hse1 complex on a membrane show how the complex binds cooperatively to lipids and ubiquitinated membrane proteins and acts as a scaffold for ubiquitination reactions.

MeSH Terms
Amino Acid Sequence Chromatography, Gel Crystallography, X-Ray Endosomal Sorting Complexes Required for Transport Immunoprecipitation Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Mutation/genetics Protein Binding Protein Structure, Tertiary Protein Transport Receptors, Cytoplasmic and Nuclear/chemistry,genetics,metabolism Saccharomyces cerevisiae/chemistry,genetics Saccharomyces cerevisiae Proteins/chemistry,genetics,metabolism Sequence Homology, Amino Acid Ubiquitin/metabolism Vesicular Transport Proteins/chemistry,genetics,metabolism
Chemicals
Endosomal Sorting Complexes Required for Transport Hse1 protein, S cerevisiae Receptors, Cytoplasmic and Nuclear Saccharomyces cerevisiae Proteins Ubiquitin VPS27 protein, S cerevisiae Vesicular Transport Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Prag Gali
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA.
Watson Hadiya
Kim Young C
Beach Bridgette M
Ghirlando Rodolfo
Hummer Gerhard
Bonifacino Juan S
Hurley James H
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1534-5807
DOI
10.1016/j.devcel.2007.04.013
Published
2007-06-00
Pages
973-86
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC2292400
Subset
IM
Grants
Intramural NIH HHS · Z01 DK036118-14 · United States
Intramural NIH HHS · Z01 DK036126-01 · United States
External Links
PubMed source DOI: 10.1016/j.devcel.2007.04.013 PMC Full Text View journal details
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