G蛋白偶联受体
受体
低温电子显微
药物发现
生物
生物物理学
计算生物学
结构生物学
化学
细胞生物学
生物信息学
生物化学
作者
Michael J. Robertson,Makaía M. Papasergi-Scott,Feng He,Alpay B. Seven,Justin Meyerowitz,Ouliana Panova,Maria Claudia Peroto,Tao Che,Georgios Skiniotis
标识
DOI:10.1038/s41594-022-00859-8
摘要
Cryogenic electron microscopy (cryo-EM) has widened the field of structure-based drug discovery by allowing for routine determination of membrane protein structures previously intractable. Despite representing one of the largest classes of therapeutic targets, most inactive-state G protein-coupled receptors (GPCRs) have remained inaccessible for cryo-EM because their small size and membrane-embedded nature impedes projection alignment for high-resolution map reconstructions. Here we demonstrate that the same single-chain camelid antibody (nanobody) recognizing a grafted intracellular loop can be used to obtain cryo-EM structures of inactive-state GPCRs at resolutions comparable or better than those obtained by X-ray crystallography. Using this approach, we obtained structures of neurotensin 1 receptor bound to antagonist SR48692, μ-opioid receptor bound to alvimopan, apo somatostatin receptor 2 and histamine receptor 2 bound to famotidine. We expect this rapid, straightforward approach to facilitate the broad exploration of GPCR inactive states without the need for extensive engineering and crystallization.
科研通智能强力驱动
Strongly Powered by AbleSci AI