Interaction of Extracellular Loop II of κ-OpioidReceptor (196–228) with Opioid Peptide Dynorphin in MembraneEnvironments as Revealed by Solid State Nuclear Magnetic Resonance,Quartz Crystal Microbalance and Molecular Dynamics Simulation.
- Resource Type
- Article
- Authors
- Kira, Atsushi; Javkhlantugs, Namsrai; Miyamori, Takenori; Sasaki, Yoshiyuki; Eguchi, Masayuki; Kawamura, Izuru; Ueda, Kazuyoshi; Naito, Akira
- Source
- Journal of Physical Chemistry B. Aug2014, Vol. 118 Issue 32, p9604-9612. 9p.
- Subject
- *OPIOID receptors
*EXTRACELLULAR fluid
*OPIOID peptides
*DYNORPHINS
*SOLID state chemistry
*NUCLEAR magnetic resonance spectroscopy
*QUARTZ crystal microbalances
*MOLECULAR dynamics
- Language
- ISSN
- 1520-6106
κ-Opioidreceptor is a member of the opioid receptor familyand selectively interacts with the opioid peptide dynorphin. Extracellularloop II (ECL-II) of the κ-opioid receptor displays an amphiphilichelix in membrane environments and the N-terminal α-helix ofdynorphin A(1–17) (hereafter DynA17) is inserted into the membranewith the tilt angle of 21° to the bilayer normal. ECL-II peptides(1–33), corresponding to 196–228 of κ-opioid receptorwith [1-13C]- or [3-13C]-labeled amino acidswere incorporated into large [dimyristoylphosphatidyl choline (DMPC)/dihexanoylphosphatidyl choline (DHPC) = 3, q = 3] and small bicelle(q = 1) systems. 13C direct detection with dipolar decouplingand magic angle spinning (DD-MAS) nuclear magnetic resonance (NMR)spectra were recorded, and the 13C chemical shift perturbationclearly indicated that DynA17 interacts with ECL-II at the locationof Val10–Ala15. Quartz crystal microbalance measurements wereperformed to determine the binding constant of ECL-II with DynA17and indicated that the binding constant between DynA17 and ECL-IIembedded in the lipid layer was 72 times larger than that betweenDynA17 and the lipid. The result of the molecular dynamics simulationclearly indicates that the C-terminus of DynA17 interact with theamino acid residues of the region between Val10-Gln14 of ECL-II. Theseresults suggest that DynA17 interacts with the ECL-II of the κ-opioidreceptor through a hydrophobic and short-lived electrostatic interactionwith high affinity in the outer surface of the membrane. [ABSTRACT FROM AUTHOR]