The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex. |
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Authors: | E E Fry S M Lea T Jackson J W Newman F M Ellard W E Blakemore R Abu-Ghazaleh A Samuel A M King and D I Stuart |
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Institution: | The Laboratory of Molecular Biophysics, Rex Richards Building, South Parks Road, Oxford OX1 3QU, UK. |
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Abstract: | Heparan sulfate has an important role in cell entry by foot-and-mouth disease virus (FMDV). We find that subtype O1 FMDV binds this glycosaminoglycan with a high affinity by immobilizing a specific highly abundant motif of sulfated sugars. The binding site is a shallow depression on the virion surface, located at the junction of the three major capsid proteins, VP1, VP2 and VP3. Two pre-formed sulfate-binding sites control receptor specificity. Residue 56 of VP3, an arginine in this virus, is critical to this recognition, forming a key component of both sites. This residue is a histidine in field isolates of the virus, switching to an arginine in adaptation to tissue culture, forming the high affinity heparan sulfate-binding site. We postulate that this site is a conserved feature of FMDVs, such that in the infected animal there is a biological advantage to low affinity, or more selective, interactions with glycosaminoglycan receptors. |
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Keywords: | heparan sulfate protein–carbohydrate interactions virus–receptor interactions virus structure X-ray crystallography |
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