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DOI | 10.1126/science.aau5595 |
Molecular basis for high-affinity agonist binding in GPCRs | |
Warne, Tony1; Edwards, Patricia C.1; Dore, Andrew S.2; Leslie, Andrew G. W.1; Tate, Christopher G.1 | |
2019-05-24 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6442页码:775-+ |
文章类型 | Article |
语种 | 英语 |
国家 | England |
英文摘要 | G protein-coupled receptors (GPCRs) in the G protein-coupled active state have higher affinity for agonists as compared with when they are in the inactive state, but the molecular basis for this is unclear. We have determined four active-state structures of the beta(1)-adrenoceptor (beta(1)AR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy. Comparison with inactive-state structures of b1AR bound to the identical ligands showed a 24 to 42% reduction in the volume of the orthosteric binding site. Potential hydrogen bonds were also shorter, and there was up to a 30% increase in the number of atomic contacts between the receptor and ligand. This explains the increase in agonist affinity of GPCRs in the active state for a wide range of structurally distinct agonists. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000469296000043 |
WOS关键词 | PROTEIN-COUPLED RECEPTORS ; LIGAND EFFICACY ; CRYSTALLIZATION ; ACTIVATION ; POCKET |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201487 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.MRC, Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England; 2.Sosei Heptares, Steinmetz Bldg,Granta Pk, Cambridge CB21 6GT, England |
推荐引用方式 GB/T 7714 | Warne, Tony,Edwards, Patricia C.,Dore, Andrew S.,et al. Molecular basis for high-affinity agonist binding in GPCRs[J]. SCIENCE,2019,364(6442):775-+. |
APA | Warne, Tony,Edwards, Patricia C.,Dore, Andrew S.,Leslie, Andrew G. W.,&Tate, Christopher G..(2019).Molecular basis for high-affinity agonist binding in GPCRs.SCIENCE,364(6442),775-+. |
MLA | Warne, Tony,et al."Molecular basis for high-affinity agonist binding in GPCRs".SCIENCE 364.6442(2019):775-+. |
条目包含的文件 | 条目无相关文件。 |
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