2N2F

Solution NMR structure of Dynorphin 1-13 bound to Kappa Opioid Receptor

Summary for 2N2F

• Entry DOI: 10.2210/pdb2n2f/pdb
• NMR Information: BMRB: 25597
• Descriptor: Dynorphin A(1-13) (1 entity in total)
• Functional Keywords: gpcr, hormone receptor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P01213
• Total number of polymer chains: 1
• Total formula weight: 1608.99

Authors

O'Connor, C.,White, K.,Doncescu, N.,Didenko, T.,Roth, B.L.,Czaplicki, G.,Stevens, R.C.,Wuthrich, K.,Milon, A. (deposition date: 2015-05-06, release date: 2015-09-09, Last modification date: 2024-05-15)

Primary citation

O'Connor, C.,White, K.L.,Doncescu, N.,Didenko, T.,Roth, B.L.,Czaplicki, G.,Stevens, R.C.,Wuthrich, K.,Milon, A.
NMR structure and dynamics of the agonist dynorphin peptide bound to the human kappa opioid receptor.
Proc.Natl.Acad.Sci.USA, 112:11852-11857, 2015

PubMed Abstract: 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 ∼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.

PubMed: 26372966
DOI: 10.1073/pnas.1510117112

Experimental method

SOLUTION NMR