4P1V

Structure of the P domain from a GI.7 Norovirus variant in complex with H-type 2 HBGA

Summary for 4P1V

• Entry DOI: 10.2210/pdb4p1v/pdb
• Related PRD ID: PRD_900036
• Descriptor: P domain of VPI, alpha-L-fucopyranose-(1-2)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: p domain, capsid protein, norovirus, hbga, h-type2, secretor, viral protein
• Biological source: Norovirus Hu/GI.7/TCH-060/USA/2003
• Total number of polymer chains: 4
• Total formula weight: 132587.76

Authors

Shanker, S.,Czako, R.,Sankaran, B.,Atmar, R.,Estes, M.,Prasad, B.V.V. (deposition date: 2014-02-27, release date: 2014-04-02, Last modification date: 2023-09-27)

Primary citation

Shanker, S.,Czako, R.,Sankaran, B.,Atmar, R.L.,Estes, M.K.,Prasad, B.V.
Structural analysis of determinants of histo-blood group antigen binding specificity in genogroup I noroviruses.
J.Virol., 88:6168-6180, 2014

PubMed Abstract: Human noroviruses (NoVs) cause acute epidemic gastroenteritis. Susceptibility to the majority of NoV infections is determined by genetically controlled secretor-dependent expression of histo-blood group antigens (HBGAs), which are also critical for NoV attachment to host cells. Human NoVs are classified into two major genogroups (genogroup I [GI] and GII), with each genogroup further divided into several genotypes. GII NoVs are more prevalent and exhibit periodic emergence of new variants, suggested to be driven by altered HBGA binding specificities and antigenic drift. Recent epidemiological studies show increased activity among GI NoVs, with some members showing the ability to bind nonsecretor HBGAs. NoVs bind HBGAs through the protruding (P) domain of the major capsid protein VP1. GI NoVs, similar to GII, exhibit significant sequence variations in the P domain; it is unclear how these variations affect HBGA binding specificities. To understand the determinants of possible strain-specific HBGA binding among GI NoVs, we determined the structure of the P domain of a GI.7 clinical isolate and compared it to the previously determined P domain structures of GI.1 and GI.2 strains. Our crystallographic studies revealed significant structural differences, particularly in the loop regions of the GI.7 P domain, altering its surface topography and electrostatic landscape and potentially indicating antigenic variation. The GI.7 strain bound to H- and A-type, Lewis secretor, and Lewis nonsecretor families of HBGAs, allowing us to further elucidate the structural determinants of nonsecretor HBGA binding among GI NoVs and to infer several contrasting and generalizable features of HBGA binding in the GI NoVs.

PubMed: 24648450
DOI: 10.1128/JVI.00201-14

Experimental method

X-RAY DIFFRACTION (1.5497 Å)