Dynamic States of the Ligand-Free Class A G Protein-Coupled Receptor Extracellular Side
文献类型：期刊论文
| 作者 | Zhang, Qiansen1; Zhou, Mang2; Zhao, Lifen2; Jiang, Hualiang2 ; Yang, Huaiyu1
|
| 刊名 | BIOCHEMISTRY
 |
| 出版日期 | 2018-08-14 |
| 卷号 | 57期号:32页码:4767-4775 |
| ISSN号 | 0006-2960 |
| DOI | 10.1021/acs.biochem.8b00146 |
| 文献子类 | Article |
| 英文摘要 | G protein-coupled receptors (GPCRs) make up the largest family of drug targets. The second extracellular loop (ECL2) and extracellular end of the third transmembrane helix (TM3) are basic structural elements of the GPCR ligand binding site. Currently, the disulfide bond between the two conserved cysteines in the ECL2 and TM3 is considered to be a basic GPCR structural feature. This disulfide bond has a significant effect on receptor dynamics and ligand binding. Here, molecular dynamics simulations and experimental results show that the two cysteines are distant from one another in the highest-population conformational state of ligand-free class A GPCRs and do not form a disulfide bond, indicating that the dynamics of the GPCR extracellular side are different from our conventional understanding. These surprising dynamics should have important effects on the drug binding process. On the basis of the two distinct ligand-free states, we suggest two kinetic processes for binding of ligands to GPCRs. These results challenge our commonly held beliefs regarding both GPCR structural features and ligand binding. |
| WOS关键词 | HUMAN P2Y(12) RECEPTOR ; CRYSTAL-STRUCTURE ; DISULFIDE BOND ; MOLECULAR-DYNAMICS ; ACTIVE METABOLITE ; FORCE-FIELD ; SURFACE EXPRESSION ; DRUG DISCOVERY ; ADP RECEPTOR ; ACTIVATION |
| 资助项目 | National Natural Science Foundation of China[21422208] ; E-Institutes of Shanghai Municipal Education Commission[E09013] ; Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund[U1501501] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000442184600002 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279620]  |
| 专题 | 生物技术药物研发中心（筹） 药物发现与设计中心 |
| 通讯作者 | Yang, Huaiyu |
| 作者单位 | 1.East China Normal Univ, Sch Life Sci, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Qiansen,Zhou, Mang,Zhao, Lifen,et al. Dynamic States of the Ligand-Free Class A G Protein-Coupled Receptor Extracellular Side[J]. BIOCHEMISTRY,2018,57(32):4767-4775. |
| APA | Zhang, Qiansen,Zhou, Mang,Zhao, Lifen,Jiang, Hualiang,&Yang, Huaiyu.(2018).Dynamic States of the Ligand-Free Class A G Protein-Coupled Receptor Extracellular Side.BIOCHEMISTRY,57(32),4767-4775. |
| MLA | Zhang, Qiansen,et al."Dynamic States of the Ligand-Free Class A G Protein-Coupled Receptor Extracellular Side".BIOCHEMISTRY 57.32(2018):4767-4775. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。