DYNORPHIN-PHOSPHOLIPID MEMBRANE INTERACTIONS - ROLE OF PHOSPHOLIPID HEADGROUP AND CHOLESTEROL

The interaction of the K-opioid receptor-selective heptadecapeptide dy norphin A(1-17) Tyr(1)-Gly-Gly-Phe-Leu(5)-Arg-Arg-Ile-Arg-Pro(10)- Lys -Leu-Lys-Trp-Asp(15)-Asn-Glu) with phospholipid membranes has been inv estigated by monitoring the leakage of the internal aqueous contents o f 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 phosphati dylserine than from phosphatidylcholine vesicles, and experiences a bl ue shift of the Trp fluorescence emission maximum in the presence of p hosphatidylserine vesicles. In the presence of phosphatidylcholine ves icles, however, the Trp fluorescence intensity is reduced without a bl ue shift. In phosphatidylserine membranes containing 10 mol% phosphati dylcholine, the intensity of the blue-shifted fluorescence is enhanced . This avid interaction of dynorphin A(1-17) with phosphatidylserine m embranes is likely to be mediated by the positively charged Arg and Ly s 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-te rminal region of dynorphin A (1-17) bends back onto the bilayer/water interphase, and that the Trp(14) residue is stabilized in a hydrophobi c pocked near the interphase by the interaction of the neighboring cha rged amino acids with the phosphate, carboxyl and amino groups on phos phatidylserine. (C) Munksgaard 1996.