Universal allosteric mechanism for g[alpha] activation by gpcrs

• Autores: Tilman Flock, Charles N. Ravarani, Dawei Sun, A. J. Venkatakrishnan, Melis Kayikci, Christopher G. Tate, Dmitry B. Veprintsev, M. Madan Babu
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 524, Nº 7564, 2015, págs. 173-179
• Idioma: inglés
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• Resumen

  • G protein-coupled receptors (GPCRs) allosterically activate heterotrimeric G proteins and trigger GDP release. Given that there are ~800 human GPCRs and 16 different G[alpha] genes, this raises the question of whether a universal allosteric mechanism governs G[alpha] activation. Here we show that different GPCRs interact with and activate G[alpha] proteins through a highly conserved mechanism. Comparison of G[alpha] with the small G protein Ras reveals how the evolution of short segments that undergo disorder-to-order transitions can decouple regions important for allosteric activation from receptor binding specificity. This might explain how the GPCR–G[alpha] system diversified rapidly, while conserving the allosteric activation mechanism.