4K5Y

Crystal structure of human corticotropin-releasing factor receptor 1 (CRF1R) in complex with the antagonist CP-376395

Summary for 4K5Y

• Entry DOI: 10.2210/pdb4k5y/pdb
• Related: 3EHS 3EHT 3EHU
• Descriptor: Corticotropin-releasing factor receptor 1, T4-Lysozyme chimeric construct, 3,6-dimethyl-N-(pentan-3-yl)-2-(2,4,6-trimethylphenoxy)pyridin-4-amine, OLEIC ACID, ... (8 entities in total)
• Functional Keywords: 7tm, gpcr, family b, signalling protein, g-protein, membrane, membrane protein, receptor
• Biological source: HOMO SAPIENS (human); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P34998
• Total number of polymer chains: 3
• Total formula weight: 156772.32

Authors

Hollenstein, K.,Kean, J.,Bortolato, A.,Cheng, R.K.Y.,Dore, A.S.,Jazayeri, A.,Cooke, R.M.,Weir, M.,Marshall, F.H. (deposition date: 2013-04-15, release date: 2013-07-17, Last modification date: 2024-11-20)

Primary citation

Hollenstein, K.,Kean, J.,Bortolato, A.,Cheng, R.K.,Dore, A.S.,Jazayeri, A.,Cooke, R.M.,Weir, M.,Marshall, F.H.
Structure of class B GPCR corticotropin-releasing factor receptor 1.
Nature, 499:438-443, 2013

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.

PubMed: 23863939
DOI: 10.1038/nature12357

Experimental method

X-RAY DIFFRACTION (2.977 Å)