Universal allosteric mechanism for Gα activation by GPCRs.
Universal allosteric mechanism for Gα activation by GPCRs.
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DOI：
10.1038/nature14663
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发表时间：
2015-08-13
期刊：
影响因子：
64.8
通讯作者：
Babu MM
中科院分区：
文献类型：
--
作者：
Flock T;Ravarani CNJ;Sun D;Venkatakrishnan AJ;Kayikci M;Tate CG;Veprintsev DB;Babu MM
G蛋白偶联受体（GPCR）变构激活异源三聚体G蛋白并触发GDP释放。鉴于有约800种人类GPCR和16种不同的Gα蛋白，是否存在一种通用的变构机制控制Gα激活？在这里，我们表明，不同的GPCR相互作用，并通过高度保守的机制激活Gα蛋白。Gα与小G蛋白Ras的比较揭示了可以经历无序-有序转变的短片段的进化如何将对受体结合特异性的变构激活重要的区域解耦。这可能解释了GPCR-Gα系统如何快速多样化，同时保留变构激活机制。
G protein-coupled receptors (GPCRs) allosterically activate heterotrimeric G proteins and trigger GDP release. Given that there are ~800 human GPCRs and 16 different Gα proteins, does a universal allosteric mechanism govern Gα activation? Here we show that different GPCRs interact and activate Gα proteins through a highly conserved mechanism. Comparison of Gα with the small G protein Ras reveals how the evolution of short segments that can undergo disorder-order transitions decouple regions important for allosteric activation from receptor binding specificity. This might explain how the GPCR-Gα system diversified rapidly, whilst conserving the allosteric activation mechanism.