posted on 2013-11-08, 00:00authored byChristopher McCullough, Minxiu Wang, Lijun Rong, Michael Caffrey
In influenza, the envelope protein hemagglutinin (HA) plays a critical role in viral entry by first binding to sialic acid
receptors on the cell surface and subsequently mediating fusion of the viral and target membranes. In this work, the
receptor binding properties of influenza A HA from different subtypes (H1 A/California/04/09, H5 A/Vietnam/1205/04, H5 A/
bar-headed goose/Qinghai/1A/05, and H9 A/Hong Kong/1073/99) have been characterized by NMR spectroscopy. Using
saturation transfer difference (STD) NMR, we find that all HAs bind to the receptor analogs 2,3-sialyllactose and 2,6-
sialyllactose, with subtle differences in the binding mode. Using competition STD NMR, we determine the receptor
preferences for the HA subtypes. We find that H5-Qinghai and H9-Hong Kong HA bind to both receptor analogs with similar
affinity. On the other hand, H1 exhibits a clear preference for 2,6-sialyllactose while H5-Vietnam exhibits a clear preference
for 2,3-sialyllactose. Together, these results are interpreted within the context of differences in both the amino acid
sequence and structures of HA from the different subtypes in determining receptor preference.
Funding
This work was partially supported by the University of Illinois at Chicago Center for Structural Biology.