Deng Xiaonan, Xin Yao, Miller Cassandra Lynn, Hamelberg Donald, Kirberger Michael, Moremen Kelley W, Hu Jian, Yang Jenny J
Department of Chemistry, Center for Diagnostics and Therapeutics and Advanced Translational Imaging Facility, Georgia State University, Atlanta, GA, 30303.
School of Science and Technology, Georgia Gwinnett College, Lawrenceville, GA 30043.
Curr Opin Physiol. 2020 Oct;17:269-277. doi: 10.1016/j.cophys.2020.08.020. Epub 2020 Sep 11.
Calcaium sensing receptors (CaSRs) play a central role in regulating extracellular calcium (Ca) homeostasis and many (patho)physiological processes. This regulation is primarily orchestrated in response to extracellular stimuli via the extracellular domain (ECD). This paper first reviews the modeled structure of the CaSR ECD and the prediction and investigation of the Ca and amino acid binding sites. Several recently solved X-ray structures are then compared to support a proposed CaSR activation model involving functional cooperativity. The review also discusses recent implications for drug development. These studies provide new insights into the molecular basis of diseases and the design of therapeutic agents that target CaSR and other family C G protein-coupled receptors (cGPCRs).
钙敏感受体（CaSRs）在调节细胞外钙（Ca）稳态及许多（病理）生理过程中发挥着核心作用。这种调节主要是通过细胞外结构域（ECD）响应细胞外刺激来精心安排的。本文首先综述了CaSR ECD的建模结构以及钙和氨基酸结合位点的预测与研究。然后比较了几个最近解析出的X射线结构，以支持一个涉及功能协同作用的CaSR激活模型。该综述还讨论了其对药物开发的最新影响。这些研究为疾病的分子基础以及针对CaSR和其他C类G蛋白偶联受体（cGPCRs）的治疗药物设计提供了新的见解。
