The Stabilities of the Soluble Ectodomain and Fusion Peptide Hairpins of the Influenza Virus Hemagglutinin Subunit II Protein Are Positively Correlated with Membrane Fusion

Biochemistry
A RanaweeraDavid P Weliky

Abstract

Cellular entry of influenza virus is mediated by the viral protein hemagglutinin (HA), which forms an initial complex of three HA1 and three HA2 subunits. Each HA2 includes a fusion peptide (FP), a soluble ectodomain (SE), and a transmembrane domain. HA1 binds to cellular sialic acids, followed by virus endocytosis, pH reduction, dissociation of HA1, and structural rearrangement of HA2 into a final trimer-of-SE hairpins. A decrease in pH also triggers HA2-mediated virus/endosome membrane fusion. SE hairpins have an interior parallel helical bundle and C-terminal strands in the grooves of the exterior of the bundle. FPs are separate helical hairpins. This study compares wild-type HA2 (WT-HA2) with G1E(FP) and I173E(SE strand) mutants. WT-HA2 induces vesicle fusion at pH 5.0, whereas the extent of fusion is greatly reduced for both mutants. Circular dichroism for HA2 and FHA2≡FP+SE constructs shows dramatic losses of stability for the mutants, including a Tm reduced by 40 °C for I173E-FHA2. This is evidence of destabilization of SE hairpins via dissociation of strands from the helical bundle, which is also supported by larger monomer fractions for mutant versus WT proteins. The G1E mutant may have disrupted FP hairpins, with cons...Continue Reading

References

Jan 1, 1992·Advances in Protein Chemistry·K P Murphy, E Freire
Jan 11, 1992·Proceedings of the National Academy of Sciences of the United States of America·E O FreedA T Panganiban
Aug 26, 1998·The EMBO Journal·M CaffreyG M Clore
Feb 12, 1999·Journal of Molecular Biology·R F EpandR M Epand
Jul 2, 1999·Journal of Structural Biology·Z N YangC C Hyde
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·J ChenD C Wiley
Jun 18, 2002·The Journal of Biological Chemistry·Toshihide KobayashiJean Gruenberg
Mar 13, 2003·Molecular Biology of the Cell·Ruben M MarkosyanGrigory B Melikyan
Nov 5, 2003·Nature Structural Biology·Heather E ParkJudith M White
Dec 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Audray HarrisAlasdair C Steven
Aug 28, 2007·Journal of the American Chemical Society·Jaime Curtis-FiskDavid P Weliky
Mar 4, 2008·Journal of Structural Biology·Masashi YamaguchiKuniaki Nagayama
Jun 24, 2008·Critical Reviews in Biochemistry and Molecular Biology·Judith M WhiteKathryn Schornberg
May 30, 2009·Archaea : an International Microbiological Journal·Laura PolitiRoberto Scandurra
Jul 16, 2009·Protein and Peptide Letters·Karen J CrossDavid A Steinhauer
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Justin L LorieauAd Bax
May 3, 2013·The Journal of General Virology·Ki Joon ChoKyung Hyun Kim
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Julien RocheAdriaan Bax
Mar 29, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Tianpeng DuMaili Liu

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