title: Influenza virus binds its host cell using multiple dynamic interactions.
abstract: Influenza virus belongs to a wide range of enveloped viruses. The major spike protein hemagglutinin binds sialic acid residues of glycoproteins and glycolipids with dissociation constants in the millimolar range [Sauter NK, et al. (1992) Biochemistry 31:9609-9621], indicating a multivalent binding mode. Here, we characterized the attachment of influenza virus to host cell receptors using three independent approaches. Optical tweezers and atomic force microscopy-based single-molecule force spectroscopy revealed very low interaction forces. Further, the observation of sequential unbinding events strongly suggests a multivalent binding mode between virus and cell membrane. Molecular dynamics simulations reveal a variety of unbinding pathways that indicate a highly dynamic interaction between HA and its receptor, allowing rationalization of influenza virus-cell binding quantitatively at the molecular level.
authors.affiliation: Department of Biology, Molecular Biophysics, Humboldt University Berlin, 10115 Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sieben
authors.forename: Christian
authors.initials: C
authors.lastname: Kappel
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.forename: Anna
authors.initials: A
authors.lastname: Wozniak
authors.forename: Christian
authors.initials: C
authors.lastname: Rankl
authors.forename: Peter
authors.initials: P
authors.lastname: Hinterdorfer
authors.forename: Helmut
authors.initials: H
authors.lastname: Grubmüller
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D018625:Microscopy, Atomic Force / Q000379:methods; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D052898:Optical Tweezers; D009975:Orthomyxoviridae / Q000378:metabolism*; D011485:Protein Binding; D012997:Solvents; D013816:Thermodynamics
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012997:Solvents