Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
Cell Mol Life Sci. 2011 Apr;68(7):1227-39. doi: 10.1007/s00018-010-0519-z. Epub 2010 Sep 11.
The luteinizing hormone receptor (LHR) is a G protein-coupled receptor (GPCR) particularly susceptible to spontaneous pathogenic gain-of-function mutations. Protein structure network (PSN) analysis on wild-type LHR and two constitutively active mutants, combined with in vitro mutational analysis, served to identify key amino acids that are part of the regulatory network responsible for propagating communication between the extracellular and intracellular poles of the receptor. Highly conserved amino acids in the rhodopsin family GPCRs participate in the protein structural stability as network hubs in both the inactive and active states. Moreover, they behave as the most recurrent nodes in the communication paths between the extracellular and intracellular sides in both functional states with emphasis on the active one. In this respect, non-conservative loss-of-function mutations of these amino acids is expected to impair the most relevant way of communication between activating mutation sites or hormone-binding domain and G protein recognition regions.
黄体生成素受体 (LHR) 是一种 G 蛋白偶联受体 (GPCR)，特别容易发生自发的致病功能获得性突变。对野生型 LHR 和两种组成性激活突变体的蛋白质结构网络 (PSN) 分析，结合体外突变分析，确定了关键的氨基酸，这些氨基酸是负责传播受体细胞外和细胞内两极之间通讯的调节网络的一部分。视紫红质家族 GPCR 中的高度保守氨基酸作为网络枢纽参与蛋白质结构稳定性，无论是在非活性状态还是活性状态下都是如此。此外，它们在两个功能状态（重点是活性状态）的细胞外和细胞内之间的通讯路径中表现为最常见的节点。在这方面，这些氨基酸的非保守功能丧失突变预计会损害激活突变位点或激素结合域与 G 蛋白识别区域之间最相关的通讯方式。
