一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Cell Research >>article
Cell Research

Cell Research

IF: 25.9
Download PDF

Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1

Published:2 January 2023 DOI: 10.1038/s41422-022-00751-6 PMID: 36588120
Ping Luo, Wenbo Feng, Shanshan Ma, Antao Dai, Kai Wu, Xianyue Chen, Qingning Yuan, Xiaoqing Cai, Dehua Yang, Ming-Wei Wang, H. Eric Xu, Yi Jiang

Abstract

G protein-coupled receptors (GPCRs) are regulated by various downstream proteins, of which the melanocortin receptor accessory protein 1 (MRAP1) is closely involved in the regulation of melanocortin receptor 2 (MC2R). Assisted by MRAP1, MC2R responds to adrenocorticotropic hormone (ACTH) and stimulates glucocorticoid biogenesis and cortisol secretion. MC2R activation plays an essential role in the hypothalamic-pituitary-adrenal (HPA) axis that regulates stress response, while its dysfunction causes glucocorticoid insufficiency- or cortisol excess-associated disorders. Here, we present a cryo-electron microscopy (cryo-EM) structure of the ACTH-bound MC2R–Gs–MRAP1 complex. Our structure, together with mutagenesis analysis, reveals a unique sharp kink at the extracellular region of MRAP1 and the ‘seat-belt’ effect of MRAP1 on stabilizing ACTH binding and MC2R activation. Mechanisms of ACTH recognition by MC2R and receptor activation are also demonstrated. These findings deepen our understanding of GPCR regulation by accessory proteins and provide valuable insights into the ab initio design of therapeutic agents targeting MC2R.

Similar articles

IF:29.9

The oxytocin receptor system: structure, function, and regulation.

Physiological reviews G. Gimpl,?F. Fahrenholz,etc Published: 1 April 2001
IF:2

Regulation of phosphatidylcholine biosynthesis by the methylation pathway in rat pituitary gland.

Hormone and Metabolic Research C Prasad, R M Edwards,etc Published: 1 August 1984
IF:1.6

Human Metabolism of Bis(2-ethylhexyl)phthalate

Analytical Letters E. Draviam,?K. H. Pearson,etc Published: 1 January 1982
鹰潭市| 都昌县| 甘德县| 乌兰察布市| 鹤壁市| 南昌市| 石泉县| 宜阳县| 临漳县| 铜陵市| 大足县| 龙陵县| 镇宁| 东平县| 天镇县| 新郑市| 温泉县| 鞍山市| 湘潭市| 津市市| 巨野县| 青岛市| 肥西县| 杭州市| 新晃| 五家渠市| 乐山市| 枣阳市| 平邑县| 抚顺县| 秦皇岛市| 南投市| 浏阳市| 达拉特旗| 遂昌县| 连山| 长葛市| 蛟河市| 盐边县| 吕梁市| 德兴市|