Evidence for effect of GM1 on opioid peptide conformation: NMR study on leucine enkephalin in ganglioside-containing isotropic phospholipid bicelles.
Enkephalins are endogenous neuropeptides that have opioid-like activities and compete with morphines for the receptor binding. The binding of these neuropeptides to membrane appears crucial since enkephalins interact with the nerve cell membranes to achieve bioactive conformations that fit onto multiple receptor sites (micro, delta, and kappa). Using NMR spectroscopy, we have determined the solution structure of the small opiate pentapeptide leucine enkephalin in the presence of isotropic phospholipid bicelles: phosphocholine bicelles (DMPC:CHAPS 1:4) and phosphocholine bicelles doped with ganglioside GM1 (DMPC:CHAPS:GM1 1:4:0.3). Bicelles containing GM1 were found to interact strongly with leucine enkephalin, whereas a somewhat weaker interaction was observed in the case of bicelles without GM1. Structure calculation from torsion angles, chemical shifts, and NOE-based distance constraints explored that the peptide could flexibly switch between several mu- and delta-selective conformations in both the bicelles though micro-selective conformations turned out to be geometrically preferred in each bicellar system. A detailed analysis of the structures presented supports the variance over the singly associated conformation of enkephalin in nerve cell membranes.
Gayen
Anindita
A
Department of Chemistry, University of Calcutta, Kolkata 700 009, India.
Mukhopadhyay
Chaitali
C
D001671:Biochemistry / Q000379:methods; D001703:Biophysics / Q000379:methods; D002462:Cell Membrane / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000737:chemistry*; D005677:G(M1) Ganglioside / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008823:Micelles; D008968:Molecular Conformation; D009474:Neurons / Q000378:metabolism; D018847:Opioid Peptides; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence / Q000379:methods
D008823:Micelles; D018847:Opioid Peptides; D010743:Phospholipids; D005677:G(M1) Ganglioside; D004743:Enkephalin, Leucine