Structure of class B GPCR corticotropin-releasing factor receptor 1

Kaspar Hollenstein, James Kean, Andrea Bortolato, Robert K. Y. Cheng, Andrew S. Doré, Ali Jazayeri, Robert M. Cooke, Malcolm Weir and Fiona H. Marshall ()
Additional contact information
Kaspar Hollenstein: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK
James Kean: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK
Andrea Bortolato: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK
Robert K. Y. Cheng: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK
Andrew S. Doré: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK
Ali Jazayeri: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK
Robert M. Cooke: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK
Malcolm Weir: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK
Fiona H. Marshall: Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK

Nature, 2013, vol. 499, issue 7459, 438-443

Abstract: 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.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature12357 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:499:y:2013:i:7459:d:10.1038_nature12357

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature12357

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().