引用本文:
【打印本页】   【HTML】   【下载PDF全文】   View/Add Comment  【EndNote】   【RefMan】   【BibTex】
←前一篇|后一篇→ 过刊浏览    高级检索
本文已被:浏览 1409次   下载 1324 本文二维码信息
码上扫一扫!
分享到: 微信 更多
GPCR A2AAR Agonist Binding and Induced Conformation Changes of Functional Switches
Xue-qin Pang,Jian-yong Liu*
Author NameAffiliationE-mail
Xue-qin Pang State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China  
Jian-yong Liu* State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China beam@dicp.ac.cn 
Abstract:
Agonist binding of A2A adenosine receptor (A2AAR) shows protective effects against in-flammatory and immune. Efforts are exerted in understanding the general mechanism and developing A2AAR selectively binding agonists. Using molecular dynamics (MD) simula-tions, we have studied the interactions between A2AAR and its agonist (adenosine), and an-alyzed the induced dynamic behaviors of the receptor. Key residues interacting with adeno-sine are identified: A632.61,I662.64, V843.32, L853.33, T883.36, F1685.29, M1775.38, L2496.51, H2506.52, and N2536.55 interacting with adenosine with affinities larger than 0.5 kcal/mol. Moreover, no interaction between adenosine and L1675.28 is observed, which supports our previous findings that L1675.28 is an antagonist specific binding reside. The dynamic be-haviors of agonist bound A2AAR are found to be different from apo-A2AAR in three typical functional switches: (i) tight “ionic lock” forms in adenosine-A2AAR, but it is in equi-librium between formation and breakage in apo-A2AAR; (ii) the “rotamer toggle switch”, T883.36/F2426.44/W2466.48, adopted different rotameric conformations in adenosine-A2AAR and apo-A2AAR; (iii) adenosine-A2AAR has a flexible intracellular loop 2 (IC2) and ɑ-helical IC3, while apo-A2AAR preferred ɑ-helical IC2 and flexible IC3. Our results indicate that agonist binding induced different conformational rearrangements of these characteristic func-tional switches in adenosine-A2AAR and apo-A2AAR.
Key words:  A2A adenosine receptor, Molecular dynamics, Adenosine, Specific binding, Conformational dynamics, Ionic lock, Rotamer toggle switch, Secondary structure
FundProject:
GPCR A2AAR腺苷受体蛋白的激动剂结合及其诱导的蛋白活性开关构象变化
庞雪芹,刘建勇*
摘要:
运用分子动力学模拟,研究了腺苷酸(激动剂)与A2AAR腺苷受体蛋白的相互作用和配体结合诱导的蛋白动力学变化.识别了与腺苷酸结合力强于0.5 kcal/mol的关键基团:A632.61,I662.64, V843.32, L853.33, T883.36, F1685.29, M1775.38, L2496.51
关键词:  A2AAR腺苷受体蛋白,分子动力学,腺苷酸,特异性结合,结构动力学,二级结构
DOI:10.1063/1674-0068/27/01/29-38
分类号: