MEMBRANE INTERACTION OF SYNTHETIC PEPTIDES RELATED TO THE PUTATIVE FUSOGENIC REGION OF PH-30-ALPHA, A PROTEIN IN SPERM-EGG FUSION

In order to investigate the relationship between structure and functio n of a putative fusogenic region of PH-30a, a protein active in sperm- egg fusion, two peptides, SFP22 and SFP23, whose sequences correspond to the residues 90-111 and 89-111 of PH-30 alpha, respectively, were c hemically synthesized. An analog of SFP23, SFP23AA, which has an Ala-A la sequence instead of the Pro-Pro sequence in SFP23, was also prepare d. The CD study indicated that SFP22 and SFP23 mainly took a p-structu re in the presence of DPPC and DPPC/DPPG (3/1) vesicles, while SFP23AA showed an or-helical pattern though the alpha-helical content calcula ted was low (25-30%). alpha-Helical CD curve was observed for these pe ptides in trifluoroethanol. The membrane-perturbing activity of SFP22 and SFP23 was weaker than that of SFP23AA. On the other hand, the memb rane-fusogenic activity of SFP22 and SFP23 to acidic phospholipid bila yers was much stronger than that of SFP23AA. All the peptides caused v ery weak cell lysis. These results are consistent with the reported sp eculation [Blobel, C. P. et al. (1992), Nature (London) 356, 248-252] that residues 90-111 of PH-30a may be the fusogenic region and suggest that the Pro-Pro sequence is one of the important factors for holding the active secondary structure of the fusogenic region of PH-30a in m embranes. (C) Munksgaard 1997.