Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, 36849-5519, USA.
Mol Cell Endocrinol. 2020 Jul 1;511:110862. doi: 10.1016/j.mce.2020.110862. Epub 2020 May 7.
G protein-coupled receptors (GPCRs) are highly conserved versatile signaling molecules located at the plasma membrane that respond to diverse extracellular signals. They regulate almost all physiological processes in the vertebrates. About 35% of current drugs target these receptors. Mutations in these genes have been identified as causes of numerous diseases. The seven transmembrane domain structure of GPCRs implies that the folding of these transmembrane proteins is extremely complicated and difficult. Indeed, many wild type GPCRs are not folded optimally. The most common defect in genetic diseases caused by GPCR mutations is misfolding and failure to reach the plasma membrane where it functions. General molecular chaperones aid the folding of all proteins, including GPCRs, by preventing aggregation, promoting folding and disaggregating small aggregates. Some GPCRs need additional receptor-specific chaperones to assist their folding. Many of these receptor-specific chaperones interact with additional receptors and alter receptor pharmacology, expanding the understanding of these chaperone proteins.
G 蛋白偶联受体（GPCRs）是高度保守的多功能信号分子，位于质膜上，可响应多种细胞外信号。它们调节脊椎动物的几乎所有生理过程。大约 35%的现有药物针对这些受体。这些基因的突变已被确定为许多疾病的原因。GPCR 具有七个跨膜结构域，这意味着这些跨膜蛋白的折叠非常复杂和困难。事实上，许多野生型 GPCR 没有被折叠成最佳状态。由 GPCR 突变引起的遗传性疾病中最常见的缺陷是错误折叠和无法到达发挥作用的质膜。一般分子伴侣通过防止聚集、促进折叠和分解小聚集体来帮助所有蛋白质（包括 GPCR）的折叠。一些 GPCR 需要额外的受体特异性伴侣来协助其折叠。许多这些受体特异性伴侣与其他受体相互作用并改变受体的药理学，从而扩大对这些伴侣蛋白的理解。
