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Publication Abstract from PubMed

The hemagglutinin (HA) surface glycoprotein promotes influenza virus entry and is the key protective antigen in natural immunity and vaccines. The HA protein is a trimeric envelope glycoprotein consisting of a globular receptor-binding domain (HA-RBD) that is inserted into a membrane fusion-mediating stalk domain. Similar to other Class I viral fusion proteins, the fusogenic stalk domain spontaneously refolds into its postfusion conformation when expressed in isolation, consistent with this domain being trapped in a metastable conformation. Using X-ray crystallography, we show that the influenza virus HA-RBD refolds spontaneously into its native, immunogenic structure even when expressed in an unglycosylated form in Escherichia coli. In the 2.10 A structure of the HA-RBD, the receptor-binding pocket is intact and its conformational epitopes are preserved. Along with recombinant HA-RBD being immunogenic and protective in ferrets, the protein binds with specificity to sera from influenza virus-infected patients. Overall, the data provide a structural basis for the rapid production of influenza vaccines in E. coli. From an evolutionary standpoint, the ability of the HA-RBD to refold spontaneously into its native conformation suggests that influenza virus acquired this domain as an insertion into an ancestral membrane-fusion domain. The insertion of independently folding domains into fusogenic stalk domains may be a common feature of Class I viral fusion proteins.

The Receptor-Binding Domain of Influenza Virus Hemagglutinin Produced in Escherichia coli Folds into its Native, Immunogenic Structure.,Dubois RM, Aguilar-Yanez JM, Mendoza-Ochoa GI, Oropeza-Almazan Y, Schultz-Cherry S, Alvarez MM, White SW, Russell CJ J Virol. 2010 Nov 10. PMID:21068239^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.