Nuclear Magnetic Resonance and Molecular Dynamics Simulation of the Interaction between Recognition Protein H7 of the Novel Influenza Virus H7N9 and Glycan Cell Surface Receptors
Name
nihms882728.pdf
Size
1.8 MB
Format
Adobe PDF
Checksum (MD5)
48fcc3d0cffdd3eb0ba2f1d47beee9e2
Author(s)
Macchi, Eleonora
Rudd, Timothy R.
Raman, Rahul
Sasisekharan, Ram
Yates, Edwin A.
Naggi, Annamaria
Guerrini, Marco
Elli, Stefano
Date Issued
December 2016
Journal
Biochemistry
Publisher
American Chemical Society (ACS)
Citation
Macchi, Eleonora et al. “Nuclear Magnetic Resonance and Molecular Dynamics Simulation of the Interaction Between Recognition Protein H7 of the Novel Influenza Virus H7N9 and Glycan Cell Surface Receptors.” Biochemistry 55, 48 (November 2016): 6605–6616 © 2016 American Chemical Society
Version
Author's final manuscript
Abstract
Avian influenza A viruses, which can also propagate between humans, present serious pandemic threats, particularly in Asia. The specificity (selectivity) of interactions between the recognition protein hemagglutinin (HA) of the virus capsid and the glycoconjugates of host cells also contributes to the efficient spread of the virus by aerosol between humans. Some avian origin viruses, such as H1N1 (South Carolina 1918), have improved their selectivity for human receptors by mutation in the HA receptor binding site, to generate pandemic viruses. Molecular details and dynamics of glycan-HA interactions are of interest, both in predicting the pandemic potential of a new emerging strain and in searching for new antiviral drugs. Two complementary techniques,1H saturation transfer difference (1H STD) nuclear magnetic resonance and molecular dynamics (MD) simulation, were applied to analyze the interaction of the new H7 (A/Anhui/1/13 H7N9) with LSTa [Neu5Ac α(2→3) Gal β(1→3) GlcNAc β(1→3) Gal β(1→4) Glc] and LSTc [Neu5Ac α(2→6) Gal β(1→4) GlcNAc β(1→3) Gal β(1→4) Glc] pentasaccharides, models of avian and human receptor glycans. Their interactions with H7 were analyzed for the first time using1H STD and MD, revealing structural and dynamic behavior that could not be obtained from crystal structures, and contributing to glycan-HA specificity. This highlighted aspects that could affect glycan-HA recognition, including the mutation H7 G228S, which increases H2 and H3 specificity for the human receptor. Finally, interactions between LSTc and H7 were compared with those between LSTc and H1 of H1N1 (South Carolina 1918), contributing to our understanding of the recognition ability of HAs.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/ACS.BIOCHEM.6B00693
