FUSION PEPTIDE/MEMBRANE INTERACTIONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Viral fusion is mediated by fusion proteins. Although new models have been postulated for initial interactions between fusion proteins and host membranes, the details of how fusion peptides affect the dynamic structure of the bilayers and how the fusion is triggered are still not clear. We suggest that the viral fusion is triggered by hardening (as a result of dehydration) of the outer leaflet of the bilayer, while the inner leaflet remains fluid. The dehydration of the membrane is reflected in the increase of the membrane ordering. We collected and simulated ESR spectra of chain spin labels 5PC, 14PC and a head group spin label DPP-Tempo in DMPC dispersions after addition of different amounts of the wild-type fusion peptide (wt20) of influenza hemagglutinin (HA). The order parameters of all the three spin labels increase with the concentration of wt20 added. When the concentration of wt20 further increases, the order parameter keeps increasing significantly. The increases of order parameter of 5PC and DPP-Tempo with concentration of wt20 show a similar pattern as that of 14PC, but tends to level off as DMPC/wt20 ratio is less than 600. We found that binding of wt20 to DMPC bilayers has almost no effect on the motional rates of the bilayers.