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3ehs
From Proteopedia
| 3ehs, resolution 2.76Å () | |||||||||
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| Related: | 3eht, 3ehu | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystal structure of the extracellular domain of human corticotropin releasing factor receptor type 1 (CRFR1)
The bimolecular interaction between corticotropin releasing factor (CRF), a neuropeptide, and its type-1 receptor (CRFR1), a Class B G-protein coupled receptor (GPCR), is crucial for activation of the hypothalamic-pituitary-adrenal axis in response to stress, and has been a target of intense drug design for the treatment of anxiety, depression, and related disorders. As a Class B GPCR, CRFR1 contains an N-terminal extracellular domain (ECD) that provides the primary ligand binding determinants. Here, we present three crystal structures of the human CRFR1 ECD, one in a ligand-free form, and two in distinct CRF-bound states. The CRFR1 ECD adopts the a-ss-ssa fold observed for other Class B GPCR ECDs, but the N-terminal alpha-helix is significantly shorter and does not contact CRF. CRF adopts a continuous alpha-helix that docks in a hydrophobic surface of the ECD that is distinct from the peptide binding site of other Class B GPCRs, thereby providing a basis for the specificity of ligand recognition between CRFR1 and other Class B GPCRs. The binding of CRF is accompanied by clamp-like conformational changes of two loops of the receptor that anchor the CRF C-terminus, including the C-terminal amide group. These structural studies provide a molecular framework for understanding peptide binding and specificity by the CRF receptors as well as a template for designing potent and selective CRFR1 antagonists for therapeutic applications.
Molecular recognition of corticotropin releasing factor by its G protein-coupled receptor CRFR1., Pioszak AA, Parker NR, Suino-Powell K, Xu HE, J Biol Chem. 2008 Sep 17. PMID:18801728
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3EHS is a 1 chain structure of sequence from Escherichia coli, homo sapiens. Full crystallographic information is available from OCA.
Reference
- Pioszak AA, Parker NR, Suino-Powell K, Xu HE. Molecular recognition of corticotropin releasing factor by its G protein-coupled receptor CRFR1. J Biol Chem. 2008 Sep 17. PMID:18801728 doi:M805749200
Page seeded by OCA on Mon Feb 16 12:08:56 2009
Categories: Escherichia coli, homo sapiens | Pioszak, A A. | Xu, H E. | Alternative splicing | Cell membrane | Corticotropin releasing factor | Extracellular domain | G protein-coupled receptor | Glycoprotein | Mbp fusion | Membrane | Membrane protein | Periplasm | Phosphoprotein | Receptor | Scr fold | Sugar transport | Transducer | Transmembrane | Transport
