Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis

David E. Coleman, Albert M. Berghuis, Ethan Lee, Maurine E. Linder, Alfred G. Gilman, Stephen R. Sprang

Research output: Contribution to journalArticle

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Abstract

Mechnanisms of guanosine triphosphate (GTP) hydrolysis by members of the G protein α subunit-p21ras superfamily of guanosine triphosphatases have been studied extensively but have not been well understood. High-resolution x-ray structures of the GTPγS and GDP·AlF4 - complexes formed by the G protein Giα1 demonstrate specific roles in transition-state stabilization for two highly conserved residues. Glutamine204 (GIn61 in p21ras) stabilizes and orients the hydrolytic water in the trigonal-bipyramidal transition state. Arginine 178 stabilizes the negative charge at the equatorial oxygen atoms of the pentacoordinate phosphate intermediate. Conserved only in the Gα family, this residue may account for the higher hydrolytic rate of Gα proteins relative to those of the p21ras family members The fold of Giα1 differs from that of the homologous G subunit in the conformation of a helix-loop sequence located in the α-helical domain that is characteristic of these proteins; this site may participate in effector binding. The amino-terminal 33 residues are disordered in GTPγS-Giα1, suggesting a mechanism that may promote release of the βγ subunit complex when the α subunit is activated by GTP.

Original languageEnglish (US)
Pages (from-to)1405-1412
Number of pages8
JournalScience
Volume265
Issue number5177
StatePublished - Sep 2 1994

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Guanosine Triphosphate
GTP-Binding Proteins
Hydrolysis
Guanosine
Protein Subunits
Arginine
Phosphates
X-Rays
Oxygen
Water
Proteins

ASJC Scopus subject areas

  • General

Cite this

Coleman, D. E., Berghuis, A. M., Lee, E., Linder, M. E., Gilman, A. G., & Sprang, S. R. (1994). Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis. Science, 265(5177), 1405-1412.

Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis. / Coleman, David E.; Berghuis, Albert M.; Lee, Ethan; Linder, Maurine E.; Gilman, Alfred G.; Sprang, Stephen R.

In: Science, Vol. 265, No. 5177, 02.09.1994, p. 1405-1412.

Research output: Contribution to journalArticle

Coleman, DE, Berghuis, AM, Lee, E, Linder, ME, Gilman, AG & Sprang, SR 1994, 'Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis', Science, vol. 265, no. 5177, pp. 1405-1412.
Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR. Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis. Science. 1994 Sep 2;265(5177):1405-1412.
Coleman, David E. ; Berghuis, Albert M. ; Lee, Ethan ; Linder, Maurine E. ; Gilman, Alfred G. ; Sprang, Stephen R. / Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis. In: Science. 1994 ; Vol. 265, No. 5177. pp. 1405-1412.
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