Structural study of the interaction between the SIV fusion peptide and model membranes.
It has been shown that there is a correlation between the fusogenecity of synthetic peptides corresponding to the N-terminal segment of wild-type and mutant forms of simian immunodeficiency virus gp32 (SIV) and their mode of insertion into lipid bilayers. Fusogenic activity is only observed when the peptide inserts into the bilayer with an oblique orientation. Since bilayer destabilization is a necessary step in membrane fusion, we investigate how fusion peptides, which insert at different orientations into lipid bilayers, structurally affect model membranes. We use X-ray diffraction to investigate the structural effects of two synthetic peptides on three different lipid systems. One peptide corresponds to the wild-type sequence (SIVwt), which inserts into the membrane at an oblique angle and is fusogenic. The other peptide has a rearranged sequence (SIVmutV), inserts into the membrane along the bilayer normal, and is nonfusogenic. Our results are expressed through different structural effects, which depend on the lipid system: for example, (i) disordering of the L alpha phase as evidenced by the broadening of the diffraction peaks, (ii) morphological convertion of multilamellar vesicles into unilamellar vesicles, (iii) decrease of the hexagonal phase cell parameter when SIVwt is added, and (iv) change in the conditions for the formation of cubic phases as well as its kinetic stability over a range of temperatures. Some of these observations are explicable based on the fact that the SIVwt destabilizes bilayers by inducing a negative monolayer curvature, while the SIVmutV destabilizes bilayers by inducing a positive monolayer curvature. Finally, we present a model which describes how these findings correlate with fusogenic activity and fusion inhibitory activity, respectively.
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
A
A
Colotto
I
I
Martin
J M
JM
Ruysschaert
A
A
Sen
S W
SW
Hui
R M
RM
Epand
D000595:Amino Acid Sequence; D008051:Lipid Bilayers / Q000737:chemistry*; D008969:Molecular Sequence Data; D015302:Simian Immunodeficiency Virus / Q000737:chemistry*; D014760:Viral Fusion Proteins / Q000737:chemistry*; D014961:X-Ray Diffraction
D008051:Lipid Bilayers; D014760:Viral Fusion Proteins