Structure of class B GPCR corticotropin-releasing factor receptor 1.
Hollenstein, K., Kean, J., Bortolato, A., Cheng, R.K., Dore, A.S., Jazayeri, A., Cooke, R.M., Weir, M., Marshall, F.H.(2013) Nature 499: 438-443
- PubMed: 23863939 
- DOI: https://doi.org/10.1038/nature12357
- Primary Citation of Related Structures:  
4K5Y - PubMed 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.
Organizational Affiliation: 
Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City AL7 3AX, UK.