Influenza hemagglutinins

This fusogenic activity of influenza hemagglutinin is frequently exploited in the laboratory. If, for example, the virus is bound to cells at a temperature too low for endocytosis and then the pH of the external medium is lowered, the hemagglutinin causes direct fusion of the viral envelope with the plasma membrane infection is achieved without endocytosis. Similarly, artificial vesicles with hemagglutinin in their membrane and other molecules in their lumen can be caused to fuse with cells by first allowing the vesicles to bind to the plasma membrane via the hemagglutinin and then lowering the pH of the medium. In this way the contents of the vesicles are delivered to the recipient cell s cytoplasm. 

Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry the influenza hemagglutinin. Ann Rev Biochem 69 531-569... 

H. Oka, T. Onaga, T. Koyama, C.-T. Guo, Y. Suzuki, Y. Esumi, K. Hatano, D. Temnuma, and K. Matsuoka, Sialyl 7(2 3) lactose clusters using carbosilane dendrimer core scaffolds as influenza hemagglutinin blockers, Bioorg. Med. Chem. Lett., 18 (2008) 4405 1408. 

Okamoto S, Yoshii H, Akagi T et al (2007) Influenza hemagglutinin vaccine with poly (y-glutamic acid) nanoparticles enhances the protection against influenza virus infection through both humoral and cell-mediated immunity. Vaccine 25 8270-8278... 

Chiller JM, Feldman M Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin. J Exp Med 1983 157 1434-1447. 

Bodian, D.L., Yamasaki, R.B., Buswell, R.L., Stearns, J.F., and White, J.M. Inhibition of the fusion-inducing conformational change of influenza hemagglutinin by benzoquinones and hydroquinones. Biochemistry. 1993, 32, 2967-2978. 

Hinds et al.[26 used a helicogenic Ca-alkylproline derivative 271 in the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala-OH, which is derived from an immunogenic sequence in influenza hemagglutinin, specifically replacing the first Pro residue in the sequence. They found increased binding to a pair of monoclonal antibodies which recognize this site. 26 The insertion of C -alkyl a-amino acids into peptide systems is discussed in Section 10.3. 

Coiled-coil motifs have been known to play roles in conformational switching in natural proteins for some time (Oas and Endow, 1994). The key examples are influenza hemagglutinin (Bullough et al., 1994 Carr and Kim, 1993 Carr et al., 1997), and the heat shock transcription factor (Rabindran et al., 1993). Furthermore, an engineered form of GCN4-pl, with Asn-16 replaced by Ala, switches from dimer to trimer upon addition of... 

Carr, C. M., Chaudhry, C., and Kim, P. S. (1997). Influenza hemagglutinin is spring-loaded by a metastable native conformation. Proc. Natl. Acad. Sci. USA 94, 14306-14313. 

Hatziioannou, T., Delahaye, E., Martin, F., et al. Retroviral display of functional binding domains fused to the amino terminus of influenza hemagglutinin. Hum. Gene Ther. 10 1533-1544, 1999. 

Whereas glycodendrimers bind the influenza hemagglutinin in the micromolar range, a corresponding non-dendritic active substance requires millimolar concentrations to block the sialic acid-cleaving enzyme [39]. 

Chernomordik LV, Leikina E, Frolov V, Bronk P, Zimmerberg J (1997) An early stage of membrane fusion mediated by the low pH conformation of influenza hemagglutinin depends upon membrane lipids. J Cell Biol 136 81-93... 

Graham CM, Barnett BC, Hartlmayr I et al (1989) The structural requirements for class II (I-Ad)-restricted T cell recognition of influenza hemagglutinin B cell epitopes define T cell epitopes. Eur J Immunol 19 523-528... 

Influenza hemagglutinin and neuraminidase Induces protective immunity 212... 

Influenza hemagglutinin and neuraminidase (when used in combination with heat-labile toxin (HLT) Good response in presence of HLT 219... 

Mature capsid structure, of bacteriophage T7 procapsid assembly, 310—315 Membrane-containing isometric viruses, structures of, 60-63 Membrane fusion models, of influenza hemagglutinin (HA), 340-343... 

Procapsid/capsid structure, with herpes simplex virus 1 (HSV-1), 398 projectBjFile, 111, 112 Prokaryotic expression systems, 4-8 Escherichia coli and, 4—8 Protein folding, of influenza hemagglutinin (HA), 351-352... 

Chapman and Liljas, Fig. 8. The structure of influenza hemagglutinin (Wilson et al., 1981). The strands of the jelly-roll domain (top) are denoted 1 through 8. The color scheme is blue to red from the N terminus of chain 1 (Nt 1) to the C terminus of chain 2 (Ct 2), which is cleaved from the membrane anchor. The fusion peptide is at the N terminus of chain 2 (Nt 2). In the virus, the protein forms a trimer where the long helices are parallel to the 3-fold axis and form a stem. 

Hinterdorfer P, Baber G, Tamm LK. Reconstitution of membrane fusion sites. A total internal reflection fluorescence microscopy study of influenza hemagglutinin-mediated membrane fusion. J. Biol. Chem. 1994 269 20360-20368. 

Lai AL, Park H, White JM, Tamm LK. Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity. J. Biol. Chem. 2006 281 5760-5770. 

Gray C, Tatulian SA, Wharton SA, Tamm LK. Effect of the N-terminal glycine on the secondary structure, orientation, and interaction of the influenza hemagglutinin fusion peptide with lipid bilayers. Biophys. J. 1996 70 2275-2286. 

Han X, Tamm LK. pH-dependent self-association of influenza hemagglutinin fusion peptides in lipid bilayers. J. Mol. Biol. 2000 304 953-965. 

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