Details

Autor(en) / Beteiligte

• Hao, Ning
• Chen, Yutao
• Xia, Ming
• Tan, Ming
• Liu, Wu
• Guan, Xiaotao
• Jiang, Xi
• Li, Xuemei
• Rao, Zihe

Titel

Crystal structures of GI.8 Boxer virus P dimers in complex with HBGAs, a novel evolutionary path selected by the Lewis epitope

Ist Teil von

• Protein & cell, 2015-02, Vol.6 (2), p.101-116

Ort / Verlag

Beijing: Higher Education Press

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Human noroviruses （huNoVs） recognize histo-blood group antigens （HBGAs） as attachment factors, in which genogroup （G） I and GII huNoVs use distinct binding interfaces. The genetic and evolutionary relationships of GII huNoVs under selection by the host HBGAs have been well elucidated via a number of structural studies; however, such relationships among GI NoVs remain less clear due to the fact that the structures of HBGA-binding interfaces of only three GI NoVs with similar binding profiles are known. In this study the crystal structures of the P dimers of a Lewis-binding strain, the GI.8 Boxer virus （BV） that does not bind the A and H antigens, in complex with the Lewis b （Le^b） and Ley antigens, respectively, were determined and compared with those of the three previously known GI huNoVs, i.e. GI.1 Nor- walk virus （NV）, GI.2 FUV258 （FUV） and GI.7 TCH060 （TCH） that bind the A/HILe antigens. The HBGA binding interface of BV is composed of a conserved central binding pocket （CBP） that interacts with the β-galactose of the precursor, and a well-developed Le epitope-bind- ing site formed by five amino acids, including three consecutive residues from the long P-loop and one from the S-loop of the P1 subdomain, a feature that was not seen in the other GI NoVs. On the other hand, the H epitope/acetamido binding site observed in the other GI NoVs is greatly degenerated in BV. These data explain the evolutionary path of GI NoVs selected by the poly- morphic human HBGAs. While the CBP is conserved, the regions surrounding the CBP are flexible, providingfreedom for changes. The loss or degeneration of the H epitope/acetamido binding site and the reinforcement of the Le binding site of the GI,8 BV is a typical example of such change selected by the host Lewis epitope.