Analysis of residues near the fusion peptide in the influenza hemagglutinin structure for roles in triggering membrane fusion
| Autor: | Sudha Thoennes, John J. Skehel, William A. Langley, David A. Steinhauer, Byeong-Jae Lee, Zhu-Nan Li, Rupert J. Russell |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Conformational change Protein Conformation Endosome Membrane fusion Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus Article Cell Line Fusion peptide Viral entry Cricetinae Virology Animals Humans Trypsin Hemagglutinin Tyrosine Phylogeny Histidine chemistry.chemical_classification biology Influenza A Virus H3N2 Subtype Lipid bilayer fusion Hydrogen-Ion Concentration Recombinant Proteins Influenza HA structure Amino Acid Substitution chemistry Biochemistry Mutagenesis Site-Directed Biophysics biology.protein Glycoprotein Viral Fusion Proteins |
| Zdroj: | Virology. 370:403-414 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2007.08.035 |
| Popis: | Influenza virus entry occurs in endosomes, where acidification triggers irreversible conformational changes of the hemagglutinin glycoprotein (HA) that are required for membrane fusion. The acid-induced HA structural rearrangements have been well documented, and several models have been proposed to relate these to the process of membrane fusion. However, details regarding the role of specific residues in the initiation of structural rearrangements and membrane fusion are lacking. Here we report the results of studies on the HA of A/Aichi/2/68 virus (H3 subtype), in which mutants with changes at several ionizable residues in the vicinity of the “fusion peptide” were analyzed for their effects on the pH at which conformational changes and membrane fusion occur. A variety of phenotypes was obtained, including examples of substitutions that lead to an increase in HA stability at reduced pH. Of particular note was the observation that a histidine to tyrosine substitution at HA1 position 17 resulted in a decrease in pH at which HA structural changes and membrane fusion take place by 0.3 relative to WT. The results are discussed in relation to possible mechanisms by which HA structural rearrangements are initiated at low pH and clade-specific differences near the fusion peptide. |
| Databáze: | OpenAIRE |
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