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- Title
Structure of class B GPCR corticotropin-releasing factor receptor 1.
- Authors
Hollenstein, Kaspar; Kean, James; Bortolato, Andrea; Cheng, Robert K Y; Doré, Andrew S; Jazayeri, Ali; Cooke, Robert M; Weir, Malcolm; Marshall, Fiona H
- Abstract
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 in complex 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.
- Publication
Nature, 2013, Vol 499, Issue 7459, p438
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature12357