Attachment of norovirus to histo blood group antigens: a cooperative multistep process.
Human noroviruses recognize histo blood group antigens (HBGAs) as cellular attachment factors. Recently, it has been discovered that norovirus infection can be significantly enhanced by HBGA binding. Yet the attachment process and how it promotes host-cell entry is only poorly understood. The binding of a norovirus protruding (P) domain of a predominant GII.4 Saga strain to HBGAs at atomic resolution was studied. So far, independent and equivalent multiple binding sites were held responsible for attachment. Using NMR experiments we show that norovirus-HBGA binding is a cooperative multi-step process, and native mass spectrometry reveals four instead of two HBGA binding sites per P-dimer. An accompanying crystallographic study has disclosed four instead of two L-fucose binding sites per P-dimer of a related GII.10 strain1 further supporting our findings. We have uncovered a novel paradigm for norovirus-HBGA recognition that will inspire further studies into norovirus-host interactions.
Center of Structural and Cell Biology in Medicine, Institute of Chemistry, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck (Germany).
Alvaro
A
Mallagaray
Dynamics of Viral Structures, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg (Germany).|Sample Environment Group, European XFEL GmbH, Notkestrasse 85, 22607 Hamburg (Germany).
Julia
J
Lockhauserbäumer
Schaller Research Group at the University of Heidelberg and the DKFZ, 69120 Heidelberg (Germany).|Department of Infectious Diseases and Virology, University of Heidelberg, 69120 Heidelberg (Germany).
Grant
G
Hansman
Dynamics of Viral Structures, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg (Germany).|Sample Environment Group, European XFEL GmbH, Notkestrasse 85, 22607 Hamburg (Germany).
Charlotte
C
Uetrecht
Center of Structural and Cell Biology in Medicine, Institute of Chemistry, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck (Germany). thomas.peters@chemie.uni-luebeck.de.
Thomas
T
Peters
D001665:Binding Sites; D001789:Blood Group Antigens / Q000737:chemistry / Q000378:metabolism*; D017250:Caliciviridae Infections / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D062105:Molecular Docking Simulation; D029322:Norovirus / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding
D001789:Blood Group Antigens
NMR spectroscopy; carbohydrates; cooperative binding; multivalency; native mass spectrometry