Structural Basis for the Recognition of Blood Group Trisaccharides by Norovirus

Abstract

Noroviruses are one of the major causes of nonbacterial gastroenteritis epidemics in humans. Recent studies on norovirus receptors show that different noroviruses recognize different human histo-blood group antigens (HBGAs), and eight receptor binding patterns of noroviruses have been identified. The P domain of the norovirus capsids is directly involved in this recognition. To determine the precise locations and receptor binding modes of HBGA carbohydrates on the viral capsids, a recombinant P protein of a GII-4 strain norovirus, VA387, was cocrystallized with synthetic type A or B trisaccharides. Based on complex crystal structures observed at a 2.0-Å resolution, we demonstrated that the receptor binding site lies at the outermost end of the P domain and forms an extensive hydrogen-bonding network with the saccharide ligand. The A and B trisaccharides display similar binding modes, and the common fucose ring plays a key role in this interaction. The extensive interface between the two protomers in a P dimer also plays a crucial role in the formation of the receptor binding interface.

Quasispecies dynamics and molecular evolution of human norovirus capsid P region during chronic infection

“…When comparing the potential trisaccharide A and B interacting positions (343-345 and 374) (Cao et al, 2007), we found residues 344 (Val), 345 (Phe) and 374 (Pro) to be ACR in all partitions, and residue 343 to be class-specific from partition II to partition X. A second plausible binding pocket (except from the one located in the domain interface) includes residues 390-392, 395 and 344 (Cao et al, 2007).…”

“…Cao and coworkers have previously proposed from crystal structure studies that residues involved in binding of A and B trisaccharide to the P2 domain of GII.4 virus (VA387 strain), located at the dimer interface, are 343 (Ser), 344 (Thr), 345 (Arg) and 374 (Asp) from one protomer and 441 (Ser), 442 (Gly) and 443 (Tyr) in the other (Cao et al, 2007). The amino acids at the corresponding position of the first protomer in GII.3 were investigated and all found to be ACR; in chronological order: 356 (Thr), 357 (Thr), 358 (Arg) and 386 (Asp) (Fig.…”

“…Each capsid protein is folded into two major domains, the S (shell) and the P (protruding) domains that are connected via an eight aa hinge region. The P domain is further subdivided into P1-1, P1-2 and P2, the last located on the most exterior part of the capsid and therefore predicted to bear antigenic determinants affecting the immunological response and host specificity, including the receptor-binding pocket (Cao et al, 2007;Prasad et al, 1999).…”

Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding

“…Superimposition of P2 and P1 by Dali server yields a Z score of 2.1. P2 is also homologous to the receptor binding domain of norovirus in the Caliciviridae family (Z score ϭ 2.0) (25). Noroviruses use blood-group trisaccharides as cell receptors.…”

Chimpanzees as an animal model for human norovirus infection and vaccine development

“…The NV protruding (P) domain of the VP1 capsid protein was cocrystallized with certain saccharides of the histo-blood group antigens (HBGAs), following a proposed association of HBGA binding with viral entry into epithelial cells of the gastrointestinal tract (9). The amino acids involved in this interaction were identified, and two sites (interaction sites 1 and 2) that participate in trisaccharide A and B binding were mapped (10,11).…”