2ZL6

Atomic resolution structural characterization of recognition of histo-blood group antigens by Norwalk virus

Summary for 2ZL6

• Entry DOI: 10.2210/pdb2zl6/pdb
• Related: 2ZL5 2ZL7
• Descriptor: 58 kd capsid protein, alpha-L-fucopyranose-(1-2)-beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: norovirus, norwalk virus, hbga, histo-blood group antigen, carbohydrate, vp1, p-domain, viral protein
• Biological source: Norwalk virus
• Cellular location: Virion: Q83884
• Total number of polymer chains: 2
• Total formula weight: 64020.03

Authors

Choi, J.M.,Huston, A.M.,Estes, M.K.,Prasad, B.V.V. (deposition date: 2008-04-02, release date: 2008-07-22, Last modification date: 2023-11-01)

Primary citation

Choi, J.M.,Hutson, A.M.,Estes, M.K.,Prasad, B.V.V.
Atomic resolution structural characterization of recognition of histo-blood group antigens by Norwalk virus
Proc.Natl.Acad.Sci.Usa, 105:9175-9180, 2008

PubMed Abstract: Members of Norovirus, a genus in the family Caliciviridae, are causative agents of epidemic diarrhea in humans. Susceptibility to several noroviruses is linked to human histo-blood type, and its determinant histo-blood group antigens (HBGAs) are regarded as receptors for these viruses. Specificity for these carbohydrates is strain-dependent. Norwalk virus (NV) is the prototype genogroup I norovirus that specifically recognizes A- and H-type HBGA, in contrast to genogroup II noroviruses that exhibit a more diverse HBGA binding pattern. To understand the structural basis for how HBGAs interact with the NV capsid protein, and how the specificity is achieved, we carried out x-ray crystallographic analysis of the capsid protein domain by itself and in complex with A- and H-type HBGA at a resolution of approximately 1.4 A. Despite differences in their carbohydrate sequence and linkage, both HBGAs bind to the same surface-exposed site in the capsid protein and project outward from the capsid surface, substantiating their possible role in initiating cell attachment. Precisely juxtaposed polar side chains that engage the sugar hydroxyls in a cooperative hydrogen bonding and a His/Trp pair involved in a cation-pi interaction contribute to selective and specific recognition of A- and H-type HBGAs. This unique binding epitope, confirmed by mutational analysis, is highly conserved, but only in the genogroup I noroviruses, suggesting that a mechanism by which noroviruses infect broader human populations is by evolving different sites with altered HBGA specificities.

PubMed: 18599458
DOI: 10.1073/pnas.0803275105

Experimental method

X-RAY DIFFRACTION (1.43 Å)