The relevance of salt bridges for the stability of the influenza virus hemagglutinin
- 11 January 2007
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 21 (4) , 995-1002
Abstract
Hemagglutinin (HA) of influenza virus undergoes an irreversible conformational change at acidic pH, mediating viral fusion with the host endosomal membrane. To unravel the molecular basis of the pH‐dependent stability of HA, we demonstrate by mu‐tagenesis of the prototype HA of virus strain X31 (H3 subtype) that salt bridges, especially a tetrad salt bridge within the monomers, are crucial for folding and stability of the trimeric ectodomain. This complex (tetrad) salt bridge is highly conserved among influenza virus subtypes. Introducing additional sites of electrostatic attraction between monomers in the distal region enhanced the stability of ectodomain at low pH mimicking the natural variant H2 subtype. We propose that distinct salt bridges in the distal domain may contribute to the enhanced stability of HA of natural virus vari‐ants. This hypothesis may provide clues to understanding adaptations of virus strains (for example, avian influenza viruses) in order to preserve stability of the protein in the host‐specific environment.—Rachakonda, P. S., Veit, M., Korte, T., Ludwig, K., Böttcher, C., Huang, Q., Schmidt, M. F. G., Herrmann, A. The relevance of salt bridges for the stability of the influenza virus hemagglutinin. FASEB J. 21, 995–1002 (2007)Keywords
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