Lewis histo-blood group alpha1,3/alpha1,4 fucose residues may both mediate binding to GII.4 noroviruses
Artikel i vetenskaplig tidskrift, 2012

Human noroviruses cause recurrent epidemics of gastroenteritis known to be dominated by the clinically important GII.4 genotype which recognizes human Secretor gene-dependent ABH histo-blood group antigens (HBGAs) as attachment factors. There is increasing evidence that GII.4 noroviruses have undergone evolutionary changes to recognize Lewis antigens and non-Secretor saliva. In this study, we have investigated the possibilities of the Lewis alpha1,3/alpha1,4 fucoses as mediators of binding of GII.4 noroviruses to Lewis antigens. The study was carried out using molecular dynamics simulations of Lewis type-1 and type-2 chain HBGAs in complex with VA387 P domain dimers in explicit water. Based on the computer simulations, we suggest the possibility of two receptor binding modes for Lewis HBGAs: the "Secretor pose" with the Secretor Fucalpha1,2 in the binding site and the "Lewis pose" with the Lewis Fucalpha1,3/alpha1,4 residues in the binding site. This was further supported by an extensive GlyVicinity analysis of the Protein Data Bank with respect to the occurrence of the Lewis and Secretor poses in complexes of Lewis antigens with lectins and antibodies as well as GII norovirus strains. The Lewis pose can also explain the interactions of GII.4 norovirus strains with Le(x) and SLe(x) structures. Moreover, the present model suggests binding of complex branched polysaccharides, with the Lewis antigens at the nonreducing end, to P domain dimers of GII.4 strains. Our results are relevant for understanding the evolution of norovirus binding specificities and for in silico design of future antiviral therapeutics.

Författare

Waqas Nasir

Göteborgs universitet

M. Frank

Biognos AB

Ashok Krishna Chaitanya Koppisetty

Chalmers, Data- och informationsteknik, Datavetenskap

G. Larson

Göteborgs universitet

Per-Georg Nyholm

Göteborgs universitet

Glycobiology

0959-6658 (ISSN) 1460-2423 (eISSN)

Vol. 22 9 1163-72

Ämneskategorier

Annan klinisk medicin

Klinisk laboratoriemedicin

Annan kemi

Bioinformatik (beräkningsbiologi)

Styrkeområden

Livsvetenskaper och teknik

DOI

10.1093/glycob/cws084

PubMed

22589081

Mer information

Skapat

2017-10-07