3MLH

Crystal structure of the 2009 H1N1 influenza virus hemagglutinin receptor-binding domain

Summary for 3MLH

• Entry DOI: 10.2210/pdb3mlh/pdb
• Descriptor: Hemagglutinin, GLYCEROL (3 entities in total)
• Functional Keywords: hemagglutinin, receptor-binding domain, lectin, antigen, viral protein
• Biological source: Influenza A virus
• Total number of polymer chains: 2
• Total formula weight: 53381.41

Authors

DuBois, R.M.,Aguilar-Yanez, J.M.,Mendoza-Ochoa, G.I.,Schultz-Cherry, S.,Alvarez, M.M.,White, S.W.,Russell, C.J. (deposition date: 2010-04-16, release date: 2010-12-01, Last modification date: 2024-11-06)

Primary citation

Dubois, R.M.,Aguilar-Yanez, J.M.,Mendoza-Ochoa, G.I.,Oropeza-Almazan, Y.,Schultz-Cherry, S.,Alvarez, M.M.,White, S.W.,Russell, C.J.
The Receptor-Binding Domain of Influenza Virus Hemagglutinin Produced in Escherichia coli Folds into Its Native, Immunogenic Structure.
J.Virol., 85:865-872, 2011

PubMed Abstract: 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-Å structure of the HA-RBD, the receptor-binding pocket is intact and its conformational epitopes are preserved. Recombinant HA-RBD is immunogenic and protective in ferrets, and the protein also binds with specificity to sera from influenza virus-infected humans. 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.

PubMed: 21068239
DOI: 10.1128/JVI.01412-10

Experimental method

X-RAY DIFFRACTION (2.09 Å)