title: 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 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.
authors.affiliation: Istituto di Ricerche Chimiche e Biochimiche "G. Ronzoni" , Via Giuseppe Colombo 81, 20133 Milano, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Macchi
authors.affiliation: National Institute for Biological Standards and Control (NIBSC) , Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, U.K.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rudd
authors.affiliation: Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Rahul
authors.initials: R
authors.lastname: Raman
authors.affiliation: Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Ram
authors.initials: R
authors.lastname: Sasisekharan
authors.affiliation: Department of Biochemistry, Institute of Integrative Biology, University of Liverpool , Liverpool L69 7ZB, U.K.
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Yates
authors.affiliation: Istituto di Ricerche Chimiche e Biochimiche "G. Ronzoni" , Via Giuseppe Colombo 81, 20133 Milano, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
authors.affiliation: Istituto di Ricerche Chimiche e Biochimiche "G. Ronzoni" , Via Giuseppe Colombo 81, 20133 Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Guerrini
authors.affiliation: Istituto di Ricerche Chimiche e Biochimiche "G. Ronzoni" , Via Giuseppe Colombo 81, 20133 Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Elli
mesh_terms: D001665:Binding Sites; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism; D064766:Influenza A Virus, H7N9 Subtype / Q000378:metabolism*; D007251:Influenza, Human / Q000821:virology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D056004:Molecular Dynamics Simulation; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C109963:hemagglutinin, avian influenza A virus