tetano
Editor, Senior Moderator
Published online before print August 6, 2012, doi: 10.1073/pnas.1120265109 PNAS August 6, 2012
Influenza virus binds its host cell using multiple dynamic interactions
Christian Siebena,1,
Christian Kappelb,1,
Rong Zhuc,
Anna Wozniakd,
Christian Rankle,
Peter Hinterdorferc,
Helmut Grubm?llerb,2, and
Andreas Herrmanna,2
+ Author Affiliations
aDepartment of Biology, Molecular Biophysics, Humboldt University Berlin, 10115 Berlin, Germany;
bDepartment of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, 37077 G?ttingen, Germany;
cInstitute for Biophysics, Johannes Kepler Universit?t Linz, 4040 Linz, Austria;
dJPK Instruments Aktiengesellschaft, 12435 Berlin, Germany; and
eAgilent Technologies, 4020 Linz, Austria
Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved July 20, 2012 (received for review December 8, 2011)
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.
http://www.pnas.org/content/early/2012/07/31/1120265109.abstract
Influenza virus binds its host cell using multiple dynamic interactions
Christian Siebena,1,
Christian Kappelb,1,
Rong Zhuc,
Anna Wozniakd,
Christian Rankle,
Peter Hinterdorferc,
Helmut Grubm?llerb,2, and
Andreas Herrmanna,2
+ Author Affiliations
aDepartment of Biology, Molecular Biophysics, Humboldt University Berlin, 10115 Berlin, Germany;
bDepartment of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, 37077 G?ttingen, Germany;
cInstitute for Biophysics, Johannes Kepler Universit?t Linz, 4040 Linz, Austria;
dJPK Instruments Aktiengesellschaft, 12435 Berlin, Germany; and
eAgilent Technologies, 4020 Linz, Austria
Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved July 20, 2012 (received for review December 8, 2011)
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.
http://www.pnas.org/content/early/2012/07/31/1120265109.abstract