Crystal structure of the adenylyl cyclase activator G(sα)

Roger K. Sunahara, John J G Tesmer, Alfred G. Gilman, Stephen R. Sprang

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

The crystal structure of G(sα), the heterotrimeric G protein α subunit that stimulates adenylyl cyclase, was determined at 2.5 Å in a complex with guanosine 5'-O-(3-thio-triphosphate) (GTPγS). G(sα) is the prototypic member of a of GTP-binding proteins that regulate the activities of effectors in a hormone-dependent manner. Comparison of the structure of G(sα)·GTPγS with that of G(iα)·GTPγS suggest that their effector specificity is primarily dictated by the shape of the binding surface formed by the switch II helix and the α3-β5 loop, despite the high sequence homology of these elements. In contrast, sequence divergence explains the inability of regulators of G protein signaling to stimutate the GTPase activity of G(sα). The βγ binding surface ofG(sα) is largely conserved in sequence and structure to that of G(iα), whereas differences in the surface formed by the carboxyl-terminal helix and the α4-β6 loop may mediate ceptor specificity.

Original languageEnglish (US)
Pages (from-to)1943-1947
Number of pages5
JournalScience
Volume278
Issue number5345
DOIs
StatePublished - Dec 12 1997

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GTP-Binding Protein Regulators
Guanosine 5'-O-(3-Thiotriphosphate)
Heterotrimeric GTP-Binding Proteins
Conserved Sequence
GTP Phosphohydrolases
Protein Subunits
Sequence Homology
GTP-Binding Proteins
Adenylyl Cyclases
Hormones

ASJC Scopus subject areas

  • General

Cite this

Sunahara, R. K., Tesmer, J. J. G., Gilman, A. G., & Sprang, S. R. (1997). Crystal structure of the adenylyl cyclase activator G(sα). Science, 278(5345), 1943-1947. https://doi.org/10.1126/science.278.5345.1943

Crystal structure of the adenylyl cyclase activator G(sα). / Sunahara, Roger K.; Tesmer, John J G; Gilman, Alfred G.; Sprang, Stephen R.

In: Science, Vol. 278, No. 5345, 12.12.1997, p. 1943-1947.

Research output: Contribution to journalArticle

Sunahara, RK, Tesmer, JJG, Gilman, AG & Sprang, SR 1997, 'Crystal structure of the adenylyl cyclase activator G(sα)', Science, vol. 278, no. 5345, pp. 1943-1947. https://doi.org/10.1126/science.278.5345.1943
Sunahara RK, Tesmer JJG, Gilman AG, Sprang SR. Crystal structure of the adenylyl cyclase activator G(sα). Science. 1997 Dec 12;278(5345):1943-1947. https://doi.org/10.1126/science.278.5345.1943
Sunahara, Roger K. ; Tesmer, John J G ; Gilman, Alfred G. ; Sprang, Stephen R. / Crystal structure of the adenylyl cyclase activator G(sα). In: Science. 1997 ; Vol. 278, No. 5345. pp. 1943-1947.
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