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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.

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 ?(2?3) Gal ?(1?3) GlcNAc ?(1?3) Gal ?(1?4) Glc] and LSTc [Neu5Ac ?(2?6) Gal ?(1?4) GlcNAc ?(1?3) Gal ?(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.

SUBMITTER: Macchi E

PROVIDER: S-EPMC5559875 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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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 E Rudd Timothy R TR Raman Rahul R Sasisekharan Ram R Yates Edwin A EA Naggi Annamaria A Guerrini Marco M Elli Stefano S

Biochemistry 20161123 48

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 rec ...[more]

PMID: 27933797

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Project description:The glycan receptor binding and specificity of influenza A viral hemagglutinin (HA) are critical for virus infection and transmission in humans. However, ambiguities in the interpretation of the receptor binding specificity of hemagglutinin from human- and avian-adapted viruses have prevented an understanding of its relationship with aerosol transmissibility, an exclusive property of human-adapted viruses. A previous conformational study, which we performed, indicated that human and avian receptors sample distinct conformations in solution. On the basis of detailed nuclear magnetic resonance (NMR) studies provided herein, we offer evidence of the distinct structural constraints imposed by hemagglutinin receptor binding sites on the glycan conformational space upon binding. The hemagglutinin from the SC18 virus, which has efficient aerosol transmissibility in humans (human-adapted), imposed the most stringent constraints on the conformational space of the human glycan receptor (LSTc), compared to single (NY18) or double (AV18) amino acid HA mutants, a property correlating to the ligand-HA binding strength. This relationship was also observed for the avian-adapted HA, where the high affinity binding partner, AV18, imposed the most stringent conformational constraints on the avian receptor, compared to those imposed by NY18. In particular, it is interesting to observe how different HAs when binding to human or avian glycosidic receptors impose significantly different conformational states, in terms of the states sampled by the glycosidic backbone and/or the entire molecule shape (linear or bent), when compared to the corresponding unbound glycans. Significantly, we delineate a "characteristic NMR signature" for the human adapted hemagglutinin (SC18) binding to human glycan receptors. Therefore, the conformational space constraints imposed by the hemagglutinin receptor binding site provide a characteristic signature that could be a useful tool for the surveillance of human adaptation of other (such as H7N9 and H5N1) deadly influenza viruses.

Dataset Information

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.

Publications

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.

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