The relevance of salt bridges for the stability of the influenza virus hemagglutinin

[Sally Furniss]

The relevance of salt bridges for the stability of the influenza virus hemagglutinin

<nobr>P. Sivaramakrishna Rachakonda^*</nobr>, <nobr>Michael Veit<sup>

</sup></nobr>, <nobr>Thomas Korte^*</nobr>, <nobr>Kai Ludwig<sup>

</sup></nobr>, <nobr>Christoph Böttcher<sup>

</sup></nobr>, <nobr>Qiang Huang<sup>

</sup></nobr>, <nobr>Michael F. G. Schmidt<sup>

</sup></nobr> and <nobr>Andreas Herrmann^*^,1</nobr> [SIZE=-1] ^* Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, Institut für Biologie/Biophysik, Berlin, Germany;

<sup>

</sup> Institut für Immunologie und Molekularbiologie, Vet.-Med. Fakultät, Freie Universität Berlin, Berlin, Germany;

<sup>

</sup> Forschungszentrum für Elektronenmikroskopie, Freie Universität Berlin, Berlin, Germany; and

<sup>

</sup> State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China [/SIZE]


[SIZE=-1]¹Correspondence: Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany. E-mail: andreas.herrmann@rz.hu-berlin.de
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<!-- ABS --> Hemagglutinin (HA) of influenza virus undergoes an irreversibleconformational change at acidic pH, mediating viral fusion withthe host endosomal membrane. To unravel the molecular basisof the pH-dependent stability of HA, we demonstrate by mutagenesisof the prototype HA of virus strain X31 (H3 subtype) that saltbridges, 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 amonginfluenza virus subtypes. Introducing additional sites of electrostaticattraction between monomers in the distal region enhanced thestability of ectodomain at low pH mimicking the natural variantH2 subtype. We propose that distinct salt bridges in the distaldomain may contribute to the enhanced stability of HA of naturalvirus variants. This hypothesis may provide clues to understandingadaptations of virus strains (for example, avian influenza viruses)in order to preserve stability of the protein in the host-specificenvironment.

—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 influenzavirus hemagglutinin.

http://www.fasebj.org/cgi/content/abstract/21/4/995