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Science 10 November 1995:
Vol. 270. no. 5238, pp. 954 - 960
DOI: 10.1126/science.270.5238.954
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Research Articles

Tertiary and Quaternary Structural Changes in G Induced by GTP Hydrolysis

Mark B. Mixon,  Ethan Lee,  David E. Coleman,  Albert M. Berghuis (1),  Alfred G. Gilman,  Stephen R. Sprang (2)

Crystallographic analysis of 2.2 angstrom resolution shows that guanosine triphosphate (GTP) hydrolysis triggers conformational changes in the heterotrimeric G-protein alpha subunit, G. The switch II and switch III segments become disordered, and linker II connecting the Ras and alpha helical domains moves, thus altering the structures of potential effector and beta binding regions. Contacts between the alpha-helical and Ras domains are weakened, possibly facilitating the release of guanosine diphosphate (GDP). The amino and carboxyl termini, which contain receptor and beta binding determinants, are disordered in the complex with GTP, but are organized into a compact microdomain on GDP hydrolysis. The amino terminus also forms extensive quaternary contacts with neighboring alpha subunits in the lattice, suggesting that multimers of alpha subunits or heterotrimers may play a role in signal transduction.


M. B. Mixon, D. E. Coleman, and S. R. Sprang are in the Department of Biochemistry and E. Lee and A. G. Gilman are in the Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA. A. M. Berghuis and S. R. Sprang are also with the Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.
(1) Present address: Department of Biochemistry, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5
(2) To whom correspondence should be addressed.


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Functional Importance of the Amino Terminus of G[IMAGE].
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Selective Interaction of AGS3 with G-proteins and the Influence of AGS3 on the Activation State of G-proteins.
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   Abstract »    Full Text »    PDF »
The Importance of Structural Transitions of the Switch II Region for the Functions of Elongation Factor Tu on the Ribosome.
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »


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