3mlh
Crystal structure of the 2009 H1N1 influenza virus hemagglutinin receptor-binding domain
Structural highlights
FunctionC4RSQ3_9INFA Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.[RuleBase:RU003324][SAAS:SAAS00145386] Publication Abstract from PubMedThe 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. See AlsoReferences
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