GPCRs 组成性活性的研究进展及意义

GPCRs是体内最大的蛋白质亚家族,其活性涉及体内绝大部分重要的生理和病理进程。研究表明,GPCRs或其突变体能在无配体结合的情况下自发产生部分甚至完全活性程度的生理活性,称之为组成性活性。据此研究者提出了GPCRs激活过程中存在多个中间激活态的观点,从而丰富了配体受体相互作用的经典模型,并使组成性活性突变体(constitutive active mutant,CAM)成为研究GPCRs的新方法。本文系统介绍了组成性活性的研究历程,以及近年来利用CAM的方法研究GPCRs的结构、激活机制和活性调节的历程和进展,和体内组成性活性突变的成因和与疾病的关系,以及CAM在研究药物作用机理和新药研发中的意义。

Recent Research and its Significance of the Constitutive Activity of GPCRs

GPCRs are the largest protein subfamily in human genome,and its activity is involved in the most physiological and pathological processes in vivo.Studies have shown that,GPCRs or its mutants spontaneously exhibit partly and even full activity in the absence of ligand which named as constitutive activity.Therefore researchers proposed there exists many active states in the middle of the activation process in GPCRs to enrich the classical ligand-receptor interaction model.And constitutively active mutant(CAM) is also to be a new useful method to study GPCRs.This paper systematically describes the course and progress of CAM in recent years,included the researches of GPCRs structure,activation mechanism and activity regulation illustrated by using CAM,the researches upon the produce mechanism of CAM in vivo and its role in different disease,as well as the significance of CAM in pharmacology and new drugs development.