Influenza virus hemagglutinin structure

Elegant studies have been carried out to investigate the structural and biochemical aspects of virus-cell fusion. Although influenza virus hemagglutinin and human immunodeficiency virus (HIV) gpl20 have been the best-studied models, numerous examples of this class I type fusion mechanism have been described. These experiments have shown that fusion is initiated by the formation of a trimeric coiled-coil helix adjacent to the fusion peptide on the virus exterior, the insertion of this fusion peptide into the host cell membrane, and the subsequent formation of a six-helix bundle (Skehel and Wiley, 1998). 

Roy and coworkers have designed inhibitors of influenza virus hemagglutinin based on several different dendrimer backbones [109,110]. Using solid phase syntheses, they generated sialic acid-displaying dendrimers based on a poly-L-lysine core structure (O Fig. 17) as ligands for influenza virus hemagglutinin. These dendrimers, which bear 2, 4, 8, or 16 pendant sialic... 

An amphipathic helix is defined as a helix in which the distribution of amino acid residues forms opposing polar and nonpolar faces. It is an important structural unit included in proteins and peptides and is responsible for interaction with biological membranes to elicit their biological functions such as membrane fusion. Influenza virus hemagglutinin [1], fertilin [1], and meltrin-a [2] contain amphipathic fusion peptides, which are likely to adopt a helical conformation during the fusion reaction. To clarify the role of amphipathic peptides in membrane fusion reactions, we synthesized five types of amphipathic model peptides and examined their helix formation, membrane binding and membrane fusion activities. 

Xu R, Wilson lA. Structural characterization of an early fusion intermediate of influenza virus hemagglutinin. / Virol. 2011 85(10) 5172-5182. 

Wilce, J. A., Zeng, W., Rose, K., Craik, D. J., Jackson, D. C., 19%, IH NMR structural study of free and template-linked antigenic peptide representing the C-terminal region of the heavy chain of influenza virus hemagglutinin. BiomedPept Proteins Nucleic Acids 2 51-8. 26.0 Brien-Simpson, N. M., Ede, N. J., Brown, L. E., Swan, J., Jackson, D. C., 1997, Polymerisation of unprotected synthetic peptides a view towards synthetic peptide vaccines. J.Am. Chem. Soc. 119 1183-1188. 

Wiley, D.C., Skehel, JJ. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu. Rev. Biochem. 56 365-394, 1987. 

For enveloped viruses such as the influenza viruses it has been shown that similar binding affinities are found for the hemagglutinin (HA) Hg-and sialic acid using either isolated HA or the whole virus [37,40] using simple H NMR titration experiments. In contrast to structural proteins of non-enveloped viruses, HA is a membrane protein and thus not as rigid as proteins as part of, e.g., icosahedral particles. For the application of STD NMR... 

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