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G 蛋白偶联受体寡聚化及其功能后果的动力学。

The Dynamics of GPCR Oligomerization and Their Functional Consequences.

机构信息

McGill University, Montreal, QC, Canada.

McGill University, Montreal, QC, Canada.

出版信息

Int Rev Cell Mol Biol. 2018;338:141-171. doi: 10.1016/bs.ircmb.2018.02.005. Epub 2018 Apr 7.

Abstract

The functional importance of G protein-coupled receptor (GPCR) oligomerization remains controversial. Although obligate dimers of class C GPCRs are well accepted, the generalizability of this phenomenon is still strongly debated with respect to other classes of GPCRs. In this review, we focus on understanding the organization and dynamics between receptor equivalents and their signaling partners in oligomeric receptor complexes, with a view toward integrating disparate viewpoints into a unified understanding. We discuss the nature of functional oligomeric entities, and how asymmetries in receptor structure and function created by oligomers might have implications for receptor function as allosteric machines and for future drug discovery.

摘要

G 蛋白偶联受体 (GPCR) 寡聚化的功能重要性仍然存在争议。虽然 C 类 GPCR 的必需二聚体是公认的,但其他类 GPCR 的这种现象的普遍性仍然存在强烈争议。在这篇综述中,我们专注于理解受体等效物与其在寡聚受体复合物中的信号伴侣之间的组织和动态,以期将不同观点整合到一个统一的理解中。我们讨论了功能性寡聚实体的性质,以及由寡聚体引起的受体结构和功能的不对称性如何对受体作为变构机器的功能以及对未来药物发现产生影响。

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