A类GPCRs变构过程的保守接触重排  

Conserved contact rearrangements in class A GPCRs allosteric process

作　　者：郭凤珍 张颖[1] 张改梅[2] 吕军[1] GUO Fengzhen;ZHANG Ying;ZHANG Gaimei;LYU Jun(College of Sciences,Inner Mongolian University of Technology,Hohhot 010051,China;Department of Obstetrics and Gynecology,Hohhot No.1 Hospital,Hohhot 010050,China)

机构地区：[1]内蒙古工业大学理学院,呼和浩特010051 [2]呼和浩特市第一医院,呼和浩特010030

出　　处：《内蒙古工业大学学报（自然科学版）》2022年第3期200-208,共9页Journal of Inner Mongolia University of Technology：Natural Science Edition

基　　金：内蒙古自治区自然科学基金资助项目(2019LH01004)。

摘　　要：应用氨基酸残基间的接触得分模型,分析了包含17个A类G蛋白偶联受体(G protein-coupled receptors,GPCRs)激活态和非激活态结构的残基对接触重排的保守性。不同于在较小数据集上所发现的34对保守重排,在新数据集上仅有4对残基存在一致的位置重排,且均为由非激活态到激活态的接触减弱类型。4对保守接触重排分布在5个螺旋的8个残基位置上,涉及位置均靠近G蛋白偶联区,远离配体结合区。保守重排的8个残基附近均存在序列保守性,这一现象符合“序列决定结构”的假设。当采用绝对满足接触得分模型设定的条件时,A类GPCRs不存在自配体结合区到G蛋白偶联区的保守的共同激活路径,保守变构很可能仅发生在靠近G蛋白结合区的位置,也表明A类GPCRs的变构表现出宏观的一致性和微观的特异性特征。A contact score model between amino acid residues was applied to analyze the conservativeness of contact rearrangements for residues containing the structures of 17 class A G protein-coupled receptors(GPCRs)in the activated and inactivated states.The results showed that:1)Different from the thirty-four pairs of conservative rearrangement found by Zhou et al.,only four pairs of residues had consistent rearrangement in the new data set,and all of them were of the contact reduction type from the inactive state to active state;2)The four conserved contact rearrangement pairs were distributed over eight residue positions in five helices,and the positions involved were all close to the G protein coupling region and far from the ligand-binding region,which was highly consistent with the conclusion of Venkatakrishnan et al;3)Sequence conservation existed near the eight residues of the conserved rearrangements,which was consistent with the hypothesis that sequence determines structure and structure determines function.The results suggest that there is no conserved activation pathway from the ligand-binding region to the G-protein-coupled region in class A GPCRs under the condition of absolutely satisfying the contact score model,and the conserved allosteric effect is likely to occur only in the vicinity of the G-protein-binding region.The results also show that the allosteric properties of class A GPCRs are macroscopic consistency and microscopic specificity.These results are of great significance to understanding the activation mechanism of GPCRs and developing functional selective agonists.

关 键 词：G蛋白偶联受体 变构 接触 序列 保守性 

分 类 号：Q518.4[生物学—生物化学] Q617