Gorvin Caroline M
Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham, United Kingdom; Institute of Metabolism and Systems Research (IMSR) and Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, United Kingdom.
Prog Mol Biol Transl Sci. 2023;195:121-135. doi: 10.1016/bs.pmbts.2022.06.014. Epub 2022 Jul 13.
The calcium-sensing receptor (CaSR) is a class C GPCR that has a fundamental role in extracellular calcium homeostasis by regulating parathyroid hormone release and urinary calcium excretion. Germline mutations in the receptor cause disorders of calcium homeostasis and studies of the functional effects of these mutations has facilitated understanding of CaSR signaling and how allosteric modulators affect these responses. In the past year, five cryo-EM structures of the near full-length CaSR have been published, demonstrating how agonist-binding transmits changes in the CaSR extracellular domain to the transmembrane region to activate G proteins, and how allosteric modulators affect these structural dynamics. Additionally, several recent studies have identified CaSR interacting proteins that regulate CaSR signaling and trafficking and contribute to understanding how the receptor achieves rapid and diverse physiological responses.
钙敏感受体（CaSR）是一种C类G蛋白偶联受体（GPCR），通过调节甲状旁腺激素释放和尿钙排泄，在细胞外钙稳态中发挥着重要作用。该受体的种系突变会导致钙稳态紊乱，对这些突变功能效应的研究有助于理解CaSR信号传导以及变构调节剂如何影响这些反应。在过去一年中，已发表了近全长CaSR的五个冷冻电镜结构，展示了激动剂结合如何将CaSR细胞外结构域的变化传递到跨膜区域以激活G蛋白，以及变构调节剂如何影响这些结构动力学。此外，最近的几项研究已经鉴定出调节CaSR信号传导和运输的CaSR相互作用蛋白，这有助于理解该受体如何实现快速且多样的生理反应。
