Insights into the Human Glycan Receptor Conformation of 1918 Pandemic Hemagglutinin–Glycan Complexes Derived from Nuclear Magnetic Resonance and Molecular Dynamics Studies

• DOI: 10.1021/bi500338r
• Publication Date: 2014-05-30T18:37:05Z
• Authors: Stefano Elli; Eleonora Macchi; Timothy R. Rudd; Rahul Raman; Guillherme Sassaki; Karthik Viswanathan; Edwin A. Yates; Zachary Shriver; Annamaria Naggi; Giangiacomo Torri; Ram Sasisekharan; Marco Guerrini
• Keywords: Pandemic; Dynamics

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