NMR structure of the first extracellular domain of corticotropin releasing factor receptor 1 (ECD1-CRF-R1) complexed with a high affinity agonist.
Related Articles NMR structure of the first extracellular domain of corticotropin releasing factor receptor 1 (ECD1-CRF-R1) complexed with a high affinity agonist.
J Biol Chem. 2010 Sep 15;
Authors: Grace CR, Perrin MH, Gulyas J, Rivier JE, Vale WW, Riek R
The corticotropin releasing factor (CRF) peptide hormone family members coordinate endocrine, behavioral, autonomic and metabolic responses to stress and play important roles within the cardiovascular, gastrointestinal and central nervous systems, among others. The actions of the peptides are mediated by activation of two G-protein coupled receptors (GPCRs) of the B1 family, CRF receptors 1 and 2 (CRF-R1 and CRF-R2α,β). The recently reported 3D structures of the first extracellular domain (ECD1) of both CRF-R1 and CRF-R2β (1,2) complexed with peptide antagonists provided a starting point in understanding the binding between CRF ligands and receptors at a molecular level. We now report the 3D NMR structure of the ECD1 of human CRF-R1 complexed with a high affinity agonist, αhcCRF. In the structure of the complex, the C-terminal residues (23-41) of αhcCRF bind to the ECD1 of CRF-R1 in a helical conformation mainly along the peptide's hydrophobic face in a manner similar to that of the antagonists in their corresponding ECD1-complex structures. Unique to this study is the observation that complex formation between an agonist and the ECD1-CRF-R1 promotes the helical conformation of the N-terminus of the former, important for receptor activation (3,4).
PMID: 20843795 [PubMed - as supplied by publisher]
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PubMed