The structure of the G protein heterotrimer Giα1β1γ2

Mark A. Wall; David E. Coleman; Ethan Lee; Jorge A. Iñiguez-Lluhi; Bruce A. Posner; Alfred G. Gilman; Stephen R. Sprang

doi:10.1016/0092-8674(95)90220-1

The structure of the G protein heterotrimer G_iα1β₁γ₂

Mark A. Wall, David E. Coleman, Ethan Lee, Jorge A. Iñiguez-Lluhi, Bruce A. Posner, Alfred G. Gilman, Stephen R. Sprang

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1018 Scopus citations

Abstract

The crystallographic structure of the G protein heterotrimer G_iα1(GDP)β₁γ₂ (at 2.3 A) reveals two nonoverlapping regions of contact between α and β, an extended interface between β and nearly all of γ, and limited interaction of α with γ. The major α/β interface covers switch II of α, and GTP-induced rearrangement of switch II causes subunit dissociation during signaling. Alterations in GDP binding in the heterotrimer (compared with α-GDP) explain stabilization of the inactive conformation of α by βγ. Repeated WD motifs in β form a circularized sevenfold β propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade.

Original language	English (US)
Pages (from-to)	1047-1058
Number of pages	12
Journal	Cell
Volume	83
Issue number	6
DOIs	https://doi.org/10.1016/0092-8674(95)90220-1
State	Published - Dec 15 1995

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/0092-8674(95)90220-1

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title = "The structure of the G protein heterotrimer Giα1β1γ2",

abstract = "The crystallographic structure of the G protein heterotrimer Giα1(GDP)β1γ2 (at 2.3 A) reveals two nonoverlapping regions of contact between α and β, an extended interface between β and nearly all of γ, and limited interaction of α with γ. The major α/β interface covers switch II of α, and GTP-induced rearrangement of switch II causes subunit dissociation during signaling. Alterations in GDP binding in the heterotrimer (compared with α-GDP) explain stabilization of the inactive conformation of α by βγ. Repeated WD motifs in β form a circularized sevenfold β propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade.",

author = "Wall, {Mark A.} and Coleman, {David E.} and Ethan Lee and I{\~n}iguez-Lluhi, {Jorge A.} and Posner, {Bruce A.} and Gilman, {Alfred G.} and Sprang, {Stephen R.}",

note = "Funding Information: Acknowledgments We are grateful to Albert Berghuis, Jim Naismith, and Ward Coates for assistance with data collection and processing; to Brian Sutton and Orelia Ortiz for assistance with illustrations; to Elliott M. Ross, Eva Neer, and Mark Mixon for helpful discussion; and to Marian Stanzel for skilled technical assistance. This work was supported by National Institutes of Health (NIH) grant DK46371 and Welch Foundation grant I-1229 to (S. R. S.) and by NIH grant GM34497, American Cancer Society grant BE30-0, Welch Foundation grant I-1 271, and the Raymond and Ellen Willie Chair of Molecular Neuropharmacology (to A. G. G.).",

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doi = "10.1016/0092-8674(95)90220-1",

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AU - Wall, Mark A.

AU - Coleman, David E.

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AU - Posner, Bruce A.

AU - Gilman, Alfred G.

AU - Sprang, Stephen R.

N1 - Funding Information: Acknowledgments We are grateful to Albert Berghuis, Jim Naismith, and Ward Coates for assistance with data collection and processing; to Brian Sutton and Orelia Ortiz for assistance with illustrations; to Elliott M. Ross, Eva Neer, and Mark Mixon for helpful discussion; and to Marian Stanzel for skilled technical assistance. This work was supported by National Institutes of Health (NIH) grant DK46371 and Welch Foundation grant I-1229 to (S. R. S.) and by NIH grant GM34497, American Cancer Society grant BE30-0, Welch Foundation grant I-1 271, and the Raymond and Ellen Willie Chair of Molecular Neuropharmacology (to A. G. G.).

PY - 1995/12/15

Y1 - 1995/12/15

N2 - The crystallographic structure of the G protein heterotrimer Giα1(GDP)β1γ2 (at 2.3 A) reveals two nonoverlapping regions of contact between α and β, an extended interface between β and nearly all of γ, and limited interaction of α with γ. The major α/β interface covers switch II of α, and GTP-induced rearrangement of switch II causes subunit dissociation during signaling. Alterations in GDP binding in the heterotrimer (compared with α-GDP) explain stabilization of the inactive conformation of α by βγ. Repeated WD motifs in β form a circularized sevenfold β propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade.

AB - The crystallographic structure of the G protein heterotrimer Giα1(GDP)β1γ2 (at 2.3 A) reveals two nonoverlapping regions of contact between α and β, an extended interface between β and nearly all of γ, and limited interaction of α with γ. The major α/β interface covers switch II of α, and GTP-induced rearrangement of switch II causes subunit dissociation during signaling. Alterations in GDP binding in the heterotrimer (compared with α-GDP) explain stabilization of the inactive conformation of α by βγ. Repeated WD motifs in β form a circularized sevenfold β propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade.

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The structure of the G protein heterotrimer G_iα1β₁γ₂

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