The effect of Zn2+ on the secondary structure of a histidine-rich fusogenic peptide and its interaction with lipid membranes

Membrane fusion between uncharged lipid vesicles can be triggered by the pe ptide sequence 'B18' from the fertilization protein 'bindin', but it only p roceeds efficiently in the presence of Zn2+ ions. We studied (i) the intera ction of Zn2+ with the fusogenic peptide B18, (ii) the binding of B18 to 1- palmitoyl-2-oleoylgycero-3-phosphocholine (POPC), and (iii) the ternary sys tem POPC/B18/Zn2+. The complex formation of Zn2+ with the central histidine -rich motif of B18 appears to shift the secondary structure away from a P-s heet towards an a-helical conformation. Here we observe for the first time an essentially a-helical structure of the peptide when immersed in POPC bil ayers which appears to represent its functional fusogenic state. Infrared l inear dichroism suggests a peripheral, oblique insertion mode of B18, media ted by the hydrophobic patches along one side of the amphipathic peptide. F urthermore, the hydration level of the peptide is reduced, suggesting that the hydrophobic region of the bilayer is involved in the lipid/peptide inte ractions. The hydration capacity of the POPC/B18/Zn2+ system is distinctly smaller than that of POPC/Zn2+ without peptide. The accompanying decrease i n the number of tightly bound water molecules per lipid can be interpreted as a reduction in the repulsive 'hydration' forces, which usually prevent t he spontaneous fusion of lipid vesicles. Binding of the B18 peptide in the presence of Zn2+ effectively renders the membrane surface more hydrophobic, thus allowing fusion to proceed. (C) 2000 Elsevier Science B.V. All rights reserved.