Nankai University Science Publication: The activation and allosteric regulation mechanism of the full-length calcium-sensitive receptor CaSR

Calcium Sensitive Receptor (CaSR) belongs to the C family of G protein-coupled receptors (GPCR), which can sense subtle changes in the concentration of extracellular Ca2+

On June 4, 2021, the team of Xue Yang/Yue Shen of Nankai University published an article titled Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor in Science Advances.

Combined with functional experiments, they found that the inactive CaSR is in an open state, and Ca2+ and tryptophan can bind to the Venus flytrap (VFT) domain of CaSR, which causes the VFT domain to close and further induces the cysteine ​​of CaSR.

Negative allosteric modulator drugs can continue to bind to the activated 7TMD and induce different new modes of interactions between the 7TMD domains

Based on the high-resolution structure of the full-length ggCaSR-active, they mapped 305 missense mutations belonging to five clinical diseases into the structure, creating a heat map of disease mutation sites

Associate researcher Yang Xue and Professor Shen Yuequan of the State Key Laboratory of Medicinal Chemical Biology of Nankai University are the co-corresponding authors of this article, and Wen Tianlei, a doctoral student in the School of Life Sciences, Nankai University, is the first author of this article