2n2f

Publication Abstract from PubMed

The structure of the dynorphin (1-13) peptide (dynorphin) bound to the human kappa opioid receptor (KOR) has been determined by liquid-state NMR spectroscopy. (1)H and (15)N chemical shift variations indicated that free and bound peptide is in fast exchange in solutions containing 1 mM dynorphin and 0.01 mM KOR. Radioligand binding indicated an intermediate-affinity interaction, with a Kd of approximately 200 nM. Transferred nuclear Overhauser enhancement spectroscopy was used to determine the structure of bound dynorphin. The N-terminal opioid signature, YGGF, was observed to be flexibly disordered, the central part of the peptide from L5 to R9 to form a helical turn, and the C-terminal segment from P10 to K13 to be flexibly disordered in this intermediate-affinity bound state. Combining molecular modeling with NMR provided an initial framework for understanding multistep activation of a G protein-coupled receptor by its cognate peptide ligand.

NMR structure and dynamics of the agonist dynorphin peptide bound to the human kappa opioid receptor.,O'Connor C, White KL, Doncescu N, Didenko T, Roth BL, Czaplicki G, Stevens RC, Wuthrich K, Milon A Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11852-7. doi:, 10.1073/pnas.1510117112. Epub 2015 Sep 8. PMID:26372966^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.