Universal allosteric mechanism for G alpha activation by GPCRs

Article

关键词: MULTIPLE SEQUENCE ALIGNMENT;    G-PROTEIN ACTIVATION;    CRYSTAL-STRUCTURE;    STRUCTURAL BASIS;    SIGNAL-TRANSDUCTION;    BINDING-SITE;    WEB SERVER;    EVOLUTION;    RAS;    HELIX;   

DOI  :  10.1038/nature14663

来源: SCIE

【 摘 要 】

G protein-coupled receptors (GPCRs) allosterically activate heterotrimeric G proteins and trigger GDP release. Given that there are similar to 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.

【 授权许可】

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