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Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions | |
2012 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
卷号 | 337期号:6091页码:232-236 |
发表状态 | 已发表 |
DOI | 10.1126/science.1219218 |
摘要 | Pharmacological responses of G protein-coupled receptors (GPCRs) can be fine-tuned by allosteric modulators. Structural studies of such effects have been limited due to the medium resolution of GPCR structures. We reengineered the human A(2A) adenosine receptor by replacing its third intracellular loop with apocytochrome b(562)RIL and solved the structure at 1.8 angstrom resolution. The high-resolution structure allowed us to identify 57 ordered water molecules inside the receptor comprising three major clusters. The central cluster harbors a putative sodium ion bound to the highly conserved aspartate residue Asp(2.50). Additionally, two cholesterols stabilize the conformation of helix VI, and one of 23 ordered lipids intercalates inside the ligand-binding pocket. These high-resolution details shed light on the potential role of structured water molecules, sodium ions, and lipids/cholesterol in GPCR stabilization and function. |
URL | 查看原文 |
收录类别 | SCI |
语种 | 英语 |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:000306323500058 |
WOS关键词 | ADENOSINE A(2A) RECEPTOR ; CRYSTAL-STRUCTURE ; OPIOID RECEPTOR ; MODULATION ; RHODOPSIN ; COMPLEX ; AMILORIDE ; RESIDUES ; SITE |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120261 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Cherezov, Vadim; Stevens, Raymond C. |
作者单位 | 1.Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA 2.Receptos, San Diego, CA 92121 USA 3.Leiden Amsterdam Ctr Drug Res, Div Med Chem, NL-2300 RA Leiden, Netherlands |
推荐引用方式 GB/T 7714 | Liu, Wei,Chun, Eugene,Thompson, Aaron A.,et al. Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions[J]. SCIENCE,2012,337(6091):232-236. |
APA | Liu, Wei.,Chun, Eugene.,Thompson, Aaron A..,Chubukov, Pavel.,Xu, Fei.,...&Stevens, Raymond C..(2012).Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions.SCIENCE,337(6091),232-236. |
MLA | Liu, Wei,et al."Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions".SCIENCE 337.6091(2012):232-236. |
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