2N2F

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

2N2F の概要

• エントリーDOI: 10.2210/pdb2n2f/pdb
• NMR情報: BMRB: 25597
• 分子名称: Dynorphin A(1-13) (1 entity in total)
• 機能のキーワード: gpcr, hormone receptor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P01213
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1608.99

構造登録者

O'Connor, C.,White, K.,Doncescu, N.,Didenko, T.,Roth, B.L.,Czaplicki, G.,Stevens, R.C.,Wuthrich, K.,Milon, A. (登録日: 2015-05-06, 公開日: 2015-09-09, 最終更新日: 2024-05-15)

主引用文献

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

実験手法

SOLUTION NMR