tetano
Editor, Senior Moderator
Published ahead of print 20 March 2013, doi: 10.1128/JVI.00545-13 JVI.00545-13
Molecular basis of the receptor binding specificity switch of the hemagglutinins from the 1918 and 2009 pandemic influenza A viruses by D225G substitution
Wei Zhang1,3,
Yi Shi1,2,3,
Jianxun Qi1,
Feng Gao4,
Qing Li1,5,
Zheng Fan6,
Jinghua Yan1 and
George F. Gao1,2,3,5,7,?
+ Author Affiliations
1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
2Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China
3University of Chinese Academy of Sciences, Beijing 100049, China
4National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
5School of Life Sciences, Science and Technology University of China, Hefei, Anhui Province, 201203, China
6Core Facility, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
7National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China
ABSTRACT
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.
http://jvi.asm.org/content/early/2013/03/13/JVI.00545-13.abstract
Molecular basis of the receptor binding specificity switch of the hemagglutinins from the 1918 and 2009 pandemic influenza A viruses by D225G substitution
Wei Zhang1,3,
Yi Shi1,2,3,
Jianxun Qi1,
Feng Gao4,
Qing Li1,5,
Zheng Fan6,
Jinghua Yan1 and
George F. Gao1,2,3,5,7,?
+ Author Affiliations
1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
2Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China
3University of Chinese Academy of Sciences, Beijing 100049, China
4National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
5School of Life Sciences, Science and Technology University of China, Hefei, Anhui Province, 201203, China
6Core Facility, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
7National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China
ABSTRACT
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.
http://jvi.asm.org/content/early/2013/03/13/JVI.00545-13.abstract