13C-13C correlation spectroscopy of membrane-associated influenza virus fusion peptide strongly supports a helix-turn-helix motif and two turn conformations. J Am Chem Soc. 2009; 131:13228–13229. [PubMed: 19711890] Jaskierny et al. Page 10 Proteins. Autho

Enveloped viruses such as influenza virus are surrounded by a membrane and infection of target cells begins with joining or “fusion ” of viral and host cell membranes into a single membrane.1 Although membrane fusion is thermodynamically allowed, there is a high kinetic barrier to the fusion process. For this reason, enveloped viruses contain “fusion protein ” which catalyzes membrane fusion. For influenza virus, hemagglutinin (HA) is the fusion protein and consists of HA1 and HA2 subunits. The ~20 residues of the HA2 N-teminus are known as the influenza fusion peptide (IFP) and play a critical role in fusion. IFP is initially buried within HA while the influenza virus is endocytosed into the target cell. The low pH of the endosome (~5) triggers a conformational change of HA and the IFP is exposed and binds to the endosomal membrane with consequent fusion between the viral and endosomal membranes. This paper focuses on the IFP in the absence of the remaining fusion protein. The peptide with IFP sequence serves as a good model system to understand the role of the IFP in influenza viral fusion as evidenced by IFP-induced lipid vesicle fusion at low pH and by the strong correlation between mutation-activity relationships of IFP-induced vesicle fusion and HA-catalyzed cell membrane fusion.2 IFP is also an important system for developing and testing differen