Dimerization and ligand binding affect the structure network of A2A adenosine receptor
Dimerization and ligand binding affect the structure network of A2A adenosine receptor
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DOI：
10.1016/j.bbamem.2010.08.006
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发表时间：
2011-05-01
影响因子：
3.4
通讯作者：
Felline, Angelo
中科院分区：
文献类型：
--
作者：
Fanelli, Francesca;Felline, Angelo
G蛋白偶联受体（GPCR）是一种变构蛋白，其功能基础是螺旋束两极之间的通讯。将GPCR结构表示为相互作用的氨基酸的网络可以是一种有意义的方式来解读配体和二聚化/寡聚化对蛋白质折叠固有的分子通信的影响。在这项研究中，我们预测了可能的同源二聚体的结构的A（2A）R和二聚化的单体形式的结构网络和通信路径的影响进行了研究。本研究的结果强调了螺旋1在A（2A）R二聚化中的作用，以及螺旋1，2，6和7中高度保守的氨基酸在通过持续的枢纽行为维持A（2A）R的结构网络中的作用，以及在螺旋束的细胞外和细胞内两极之间的信息流中的作用。保守的E/DRY基序R3.50的精氨酸不参与通信路径，但作为稳定的枢纽参与结构网络，与视紫红质的非活性状态下的D3.49和E6.30连接。A（2A）R二聚化以依赖于二聚体结构的方式影响受体折叠固有的通信网络。某些架构保留最经常性的通信路径相对于单体拮抗剂结合的形式，但提高路径的数量和频率，而其他一些损害配体介导的通信网络。配体结合也影响网络。总体而言，通信网络，属于GPCR的功能动力学预计将受到配体功能，低聚物的顺序和架构的超分子组装。这篇文章是题为“腺苷受体”的特刊的一部分。(C)2010爱思唯尔有限公司版权所有。
G protein Coupled Receptors (GPCRs) are allosteric proteins whose functioning fundamentals are the communication between the two poles of the helix bundle. The representation of GPCR structures as networks of interacting amino acids can be a meaningful way to decipher the impact of ligand and of dimerization/oligomerization on the molecular communication intrinsic to the protein fold. In this study, we predicted likely homodimer architectures of the A(2A)R and investigated the effects of dimerization on the structure network and the communication paths of the monomeric form. The results of this study emphasize the roles of helix 1 in A(2A)R dimerization and of highly conserved amino acids in helices 1, 2, 6 and 7 in maintaining the structure network of the A(2A)R through a persistent hub behavior as well as in the information flow between the extracellular and intracellular poles of the helix bundle. The arginine of the conserved E/DRY motif, R3.50, is not involved in the communication paths but participates in the structure network as a stable hub, being linked to both D3.49 and E6.30 like in the inactive states of rhodopsin. A(2A)R dimerization affects the communication networks intrinsic to the receptor fold in a way dependent on the dimer architecture. Certain architectures retain the most recurrent communication paths with respect to the monomeric antagonist-bound form but enhancing path numbers and frequencies, whereas some others impair ligand-mediated communication networks. Ligand binding affects the network as well. Overall, the communication network that pertains to the functional dynamics of a GPCR is expected to be influenced by ligand functionality, oligomeric order and architecture of the supramolecular assembly. This article is part of a Special Issue entitled: "Adenosine Receptors". (C) 2010 Elsevier B.V. All rights reserved.