Structure of class B GPCR corticotropin-releasing factor receptor 1

被引：336

作者：

Hollenstein, Kaspar ^{[1
]}

Kean, James ^{[1
]}

Bortolato, Andrea ^{[1
]}

Cheng, Robert K. Y. ^{[1
]}

Dore, Andrew S. ^{[1
]}

Jazayeri, Ali ^{[1
]}

Cooke, Robert M. ^{[1
]}

Weir, Malcolm ^{[1
]}

Marshall, Fiona H. ^{[1
]}

机构：

[1] Heptares Therapeut Ltd, Welwyn Garden City AL7 3AX, Herts, England

来源：

NATURE | 2013年 / 499卷 / 7459期

关键词：

PROTEIN-COUPLED RECEPTORS; CRYSTAL-STRUCTURE; MOLECULAR RECOGNITION; PARATHYROID-HORMONE; PEPTIDE RECEPTOR; AGONIST; BINDING; THERMOSTABILIZATION; REFINEMENT; ACTIVATION;

D O I：

10.1038/nature12357

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Structural analysis of class B G-protein-coupled receptors (GPCRs), cell-surface proteins that respond to peptide hormones, has been restricted to the amino-terminal extracellular domain, thus providing little understanding of the membrane-spanning signal transduction domain. The corticotropin-releasing factor receptor type 1 is a class B receptor which mediates the response to stress and has been considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of the human corticotropin-releasing factor receptor type 1 incomplex with the small-molecule antagonist CP-376395. The structure provides detailed insight into the architecture of class B receptors. Atomic details of the interactions of the receptor with the non-peptide ligand that binds deep within the receptor are described. This structure provides a model for all class B GPCRs and may aid in the design of new small-molecule drugs for diseases of brain and metabolism.

引用

页码：438 / +

页数：8

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