The Vps27/Hse1 Complex Is a GAT Domain-Based Scaffold for Ubiquitin-Dependent Sorting

Gali Prag, Hadiya Watson, Young C. Kim, Bridgette M. Beach, Rodolfo Ghirlando, Gerhard Hummer, Juan S S. Bonifacino, James H. Hurley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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 Å 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 Å-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.

Original languageEnglish
Pages (from-to)973-986
Number of pages14
JournalDevelopmental Cell
Issue number6
StatePublished - 5 Jun 2007
Externally publishedYes


FundersFunder number
National Institutes of Health
U.S. Department of Energy
National Institute of Diabetes and Digestive and Kidney DiseasesZ01DK029033
National Institute of Child Health and Human Development
Office of Science
Basic Energy Sciences




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