Molecular basis of the receptor binding specificity switch of the hemagglutinins from the 1918 and 2009 pandemic influenza A viruses by D225G substitution----中国科学院微生物研究所

科研成果

论文题目:	Molecular basis of the receptor binding specificity switch of the hemagglutinins from the 1918 and 2009 pandemic influenza A viruses by D225G substitution
作者:	Zhang Wei, Shi Yi, Qi Jianxun, Gao Feng, Li Qing, Fan Zheng, Yan Jinghua, George F Gao
联系作者:	George F Gao
刊物名称:	Journal of virology
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卷:
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年份:	2013
影响因子:	5.324
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摘要:	Influenza A virus uses sialic acids as cell-entry receptors, and there are two main receptor forms, alpha2,6-linkage or alpha2,3-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 alpha2,6-linkage receptor. A single D225G mutation in both H1s switches receptor-binding specificity from alpha2,6-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.