[Source: US National Library of Medicine, full text: (LINK). Abstract, edited.]
J Virol. 2013 Mar 20. [Epub ahead of print]
Molecular basis of the receptor binding specificity switch of the hemagglutinins from the 1918 and 2009 pandemic influenza A viruses by D225G substitution.
Zhang W, Shi Y, Qi J, Gao F, Li Q, Fan Z, Yan J, Gao GF.
Source: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Influenza A virus uses sialic acids as cell-entry receptors, and there are two main receptor forms, α2,6-linkage or α2,3-linkage to galactose, that determine virus host ranges (mammalian or avian). The receptor binding hemagglutinins (HAs) of both 1918 and 2009 pandemic H1N1 (18H1 and 09H1, respectively) influenza A viruses preferentially bind to the human α2,6-linkage receptor. A single D225G mutation in both H1s switches receptor-binding specificity from α2,6-linkage binding to dual receptor binding. However, the molecular basis for this specificity switch is not fully understood. Here, we show via H1-ligand complex structures that the D225G substitution results in a loss of a salt bridge between amino acids D225 and K222, enabling the key Q226 residue to interact with the avian receptor, thereby obtaining dual receptor binding. This is further confirmed by a D225E mutant that retains human receptor binding specificity with the salt bridge intact.
PMID: 23514882 [PubMed - as supplied by publisher]