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

Macchi, Eleonora, Rudd, Timothy R ORCID: 0000-0003-4434-0333, Raman, Rahul, Sasisekharan, Ram, Yates, Edwin A ORCID: 0000-0001-9365-5433, Naggi, Annamaria, Guerrini, Marco and Elli, Stefano (2016) 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). pp. 6605-6616.

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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 using ¹H 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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Polysaccharides, Receptors, Cell Surface, Receptors, Virus, Hemagglutinin Glycoproteins, Influenza Virus, Magnetic Resonance Spectroscopy, Binding Sites, Protein Binding, Kinetics, Influenza, Human, Influenza A Virus, H1N1 Subtype, Molecular Dynamics Simulation, Influenza A Virus, H7N9 Subtype, Protein Domains
Depositing User:	Symplectic Admin
Date Deposited:	16 Jan 2017 10:01
Last Modified:	19 Jan 2023 07:20
DOI:	10.1021/acs.biochem.6b00693
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3005233