Structure of RGS4 bound to AlF₄^--activated G(iα1): Stabilization of the Transition State for GTP Hydrolysis

Authors

John J.G. Tesmer, Howard Hughes Medical Institute
David M. Berman, University of Texas Southwestern Medical Center
Alfred G. Gilman, University of Texas Southwestern Medical Center
Stephen R. Sprang, University of Montana

Document Type

Article

Publication Title

Cell

Publication Date

4-18-1997

Volume

89

Issue

2

Disciplines

Biology | Life Sciences

Abstract

RGS proteins are GTPase activators for heterotrimeric G proteins. We report here the 2.8 Å resolution crystal structure of the RGS protein RGS4 complexed with G(iα1)-Mg²⁺-GDP-AlF₄. Only the core domain of RGS4 is visible in the crystal. The core domain binds to the three switch regions of G(iα1), but does not contribute catalytic residues that directly interact with either GDP or AlF₄. Therefore, RGS4 appears to catalyze rapid hydrolysis of GTP primarily by stabilizing the switch regions of G(iα1), although the conserved Asn-128 from RGS4 could also play a catalytic role by interacting with the hydrolytic water molecule or the side chain of Gln-204. The binding site for RGS4 on G(iα1) is also consistent with the activity of RGS proteins as antagonists of G(α) effectors.

DOI

https://doi.org/10.1016/S0092-8674(00)80204-4

Rights

© 1997 Cell Press

Recommended Citation

Tesmer, John J.G.; Berman, David M.; Gilman, Alfred G.; and Sprang, Stephen R., "Structure of RGS4 bound to AlF₄^--activated G(iα1): Stabilization of the Transition State for GTP Hydrolysis" (1997). Biological Sciences Faculty Publications. 538.
https://scholarworks.umt.edu/biosci_pubs/538