Dynorphin-phospholipid membrane interactions: role of phospholipid head-group and cholesterol.
The interaction of the kappa-opioid receptor-selective heptadecapeptide dynorphin A(1-17) (Tyr1-Gly-Gly-Phe-Leu5-Arg-Arg-Ile-Arg-Pro10-Lys-Leu-Lys-Trp-As p15-Asn-Glu) with phospholipid membranes has been investigated by monitoring the leakage of the internal aqueous contents of liposomes, the changes in the tryptophan emission spectrum, and the collisional quenching of tryptophan fluorescence by brominated lipids. The peptide induces more extensive leakage of contents from phosphatidylserine than from phosphatidylcholine vesicles, and experiences a blue shift of the Trp fluorescence emission maximum in the presence of phosphatidylserine vesicles. In the presence of phosphatidylcholine vesicles, however, the Trp fluorescence intensity is reduced without a blue shift. In phosphatidylserine membranes containing 10 mol% phosphatidylcholine, the intensity of the blue-shifted fluorescence is enhanced. This avid interaction of dynorphin A(1-17) with phosphatidylserine membranes is likely to be mediated by the positively charged Arg and Lys groups. It is proposed that, while the N-terminus of the peptide may be embedded in the bilayer in analogy with dynorphin (1-13), the C-terminal region of dynorphin A (1-17) bends back onto the bilayer/water interphase, and that the Trp14 residue is stabilized in a hydrophobic pocked near the interphase by the interaction of the neighboring charged amino acids with the phosphate, carboxyl and amino groups on phosphatidylserine.
Cancer Research Institute, School of Medicine, University of California, San Francisco, USA.
D R
DR
Alford
V
V
Renugopalakrishnan
N
N
Duzgunes
D000595:Amino Acid Sequence; D002784:Cholesterol / Q000737:chemistry*; D004399:Dynorphins / Q000737:chemistry*; D005456:Fluorescent Dyes; D005470:Fluorometry; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry
D005456:Fluorescent Dyes; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D004399:Dynorphins; D014364:Tryptophan; D002784:Cholesterol