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

doi:10.1016/j.devcel.2007.04.013

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 journal › Article › peer-review

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 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 language	English
Pages (from-to)	973-986
Number of pages	14
Journal	Developmental Cell
Volume	12
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2007.04.013
State	Published - 5 Jun 2007
Externally published	Yes

Keywords

CELLBIO
PROTEINS

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10.1016/j.devcel.2007.04.013

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

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 {\AA} 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 {\AA}-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.",

keywords = "CELLBIO, PROTEINS",

author = "Gali Prag and Hadiya Watson and Kim, {Young C.} and Beach, {Bridgette M.} and Rodolfo Ghirlando and Gerhard Hummer and Bonifacino, {Juan S S.} and Hurley, {James H.}",

note = "Funding Information: We thank X. (Snow) Ren and W. Smith for assistance with biochemical experiments; R. Piper for strains and plasmids; J. Chrzas, J. Gonczy, M. Graham, and the entire staff of SER-CAT beamline ID-22 for user support; and Y. Ye and A. Hickman for comments on the manuscript. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract No.W-31-109-Eng-38. This research was supported by National Institutes of Health intramural support, National Institute of Diabetes and Digestive and Kidney Diseases (J.H.H. and G.H.), National Institute of Child Health and Human Development (J.S.B.), and Intramural AIDS Targeted Antiviral Program (J.H.H. and J.S.B.). ",

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doi = "10.1016/j.devcel.2007.04.013",

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pages = "973--986",

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T1 - The Vps27/Hse1 Complex Is a GAT Domain-Based Scaffold for Ubiquitin-Dependent Sorting

AU - Prag, Gali

AU - Watson, Hadiya

AU - Kim, Young C.

AU - Beach, Bridgette M.

AU - Ghirlando, Rodolfo

AU - Hummer, Gerhard

AU - Bonifacino, Juan S S.

AU - Hurley, James H.

N1 - Funding Information: We thank X. (Snow) Ren and W. Smith for assistance with biochemical experiments; R. Piper for strains and plasmids; J. Chrzas, J. Gonczy, M. Graham, and the entire staff of SER-CAT beamline ID-22 for user support; and Y. Ye and A. Hickman for comments on the manuscript. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract No.W-31-109-Eng-38. This research was supported by National Institutes of Health intramural support, National Institute of Diabetes and Digestive and Kidney Diseases (J.H.H. and G.H.), National Institute of Child Health and Human Development (J.S.B.), and Intramural AIDS Targeted Antiviral Program (J.H.H. and J.S.B.).

PY - 2007/6/5

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N2 - 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.

AB - 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.

KW - CELLBIO

KW - PROTEINS

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AN - SCOPUS:34249674993

SN - 1534-5807

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JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -

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

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Keywords

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