Membrane-induced Step in the Activation of Sendai Virus Fusion Protein
Authors: Ben-Efraim I.; Kliger Y.; Hermesh C.; Shai Y.
Source: Journal of Molecular Biology, Volume 285, Number 2, January 1999 , pp. 609-625(17)
Publisher: Academic Press
Peptides derived from conserved heptad-repeat regions of several viruses have been shown recently to inhibit virus-cell fusion. To find out their possible role in the fusion process, two biologically active heptad-repeat segments of the fusion protein (F) of Sendai virus, SV-150 (residues 150-186), and SV-473 (residues 473-495) were synthesized, fluorescently labeled and spectroscopically characterized for their structure and organization in solution and within the membrane. SV-150 was found to be 50-fold less active than SV-473 in inhibiting Sendai virus-cell fusion. Circular dichroism (CD) spectroscopy revealed that in aqueous solution, the peptides are self-associated and adopt low -helical structure. However, when the two peptides are mixed together, their -helical content significantly increases. Fluorescence studies, CD, and polarized attenuated total reflection infrared (ATR-FTIR) spectroscopy showed that both peptides, alone or as a complex, bind strongly to negatively charged and zwitterionic phospholipid membranes, dissociate therein into -helical monomers, but do not perturb the lipid packing of the membrane. The ability of the peptides to interact with each other in solution may be correlated with antiviral activity, whereas their ability to interact with the membrane, together with their location near the fusion peptide and the transmembrane domain, suggests a revision to the currently accepted model for viral-induced membrane fusion. In the revised model, in the sequence of events associated with viral entry, the two heptad-repeat sequences may assist in bringing the viral and cellular membranes closer, thus facilitating membrane fusion. Copyright 1999 Academic Press
Document Type: Research article
Affiliations: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, 76100, Israel
Publication date: 1999-01-01