Structure of RGS4 bound to AlF4 --activated G(iα1): Stabilization of the transition state for GTP hydrolysis

John J G Tesmer, David M. Berman, Alfred G. Gilman, Stephen R. Sprang

Research output: Contribution to journalArticle

650 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalCell
Volume89
Issue number2
StatePublished - Apr 18 1997

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RGS Proteins
Guanosine Triphosphate
Hydrolysis
Stabilization
GTP Phosphohydrolase Activators
Switches
Heterotrimeric GTP-Binding Proteins
Crystal structure
Binding Sites
Crystals
Molecules
Water
tetrafluoroaluminate

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Tesmer, J. J. G., Berman, D. M., Gilman, A. G., & Sprang, S. R. (1997). Structure of RGS4 bound to AlF4 --activated G(iα1): Stabilization of the transition state for GTP hydrolysis. Cell, 89(2), 251-261.

Structure of RGS4 bound to AlF4 --activated G(iα1) : Stabilization of the transition state for GTP hydrolysis. / Tesmer, John J G; Berman, David M.; Gilman, Alfred G.; Sprang, Stephen R.

In: Cell, Vol. 89, No. 2, 18.04.1997, p. 251-261.

Research output: Contribution to journalArticle

Tesmer, JJG, Berman, DM, Gilman, AG & Sprang, SR 1997, 'Structure of RGS4 bound to AlF4 --activated G(iα1): Stabilization of the transition state for GTP hydrolysis', Cell, vol. 89, no. 2, pp. 251-261.
Tesmer, John J G ; Berman, David M. ; Gilman, Alfred G. ; Sprang, Stephen R. / Structure of RGS4 bound to AlF4 --activated G(iα1) : Stabilization of the transition state for GTP hydrolysis. In: Cell. 1997 ; Vol. 89, No. 2. pp. 251-261.
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