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Publication Abstract from PubMed

Many viruses attach to target cells by binding to cell-surface glycans. To gain a better understanding of strategies used by viruses to engage carbohydrate receptors, we determined the crystal structures of reovirus attachment protein sigma1 in complex with alpha-2,3-sialyllactose, alpha-2,6-sialyllactose, and alpha-2,8-di-siallylactose. All three oligosaccharides terminate in sialic acid, which serves as a receptor for the reovirus serotype studied here. The overall structure of sigma1 resembles an elongated, filamentous trimer. It contains a globular head featuring a compact beta-barrel, and a fibrous extension formed by seven repeating units of a triple beta-spiral that is interrupted near its midpoint by a short alpha-helical coiled coil. The carbohydrate-binding site is located between beta-spiral repeats two and three, distal from the head. In all three complexes, the terminal sialic acid forms almost all of the contacts with sigma1 in an identical manner, while the remaining components of the oligosaccharides make little or no contacts. We used this structural information to guide mutagenesis studies to identify residues in sigma1 that functionally engage sialic acid by assessing hemagglutination capacity and growth in murine erythroleukemia cells, which require sialic acid binding for productive infection. Our studies using sigma1 mutant viruses reveal that residues 198, 202, 203, 204, and 205 are required for functional binding to sialic acid by reovirus. These findings provide insight into mechanisms of reovirus attachment to cell-surface glycans and contribute to an understanding of carbohydrate binding by viruses. They also establish a filamentous, trimeric carbohydrate-binding module that could potentially be used to endow other trimeric proteins with carbohydrate-binding properties.

Crystal structure of reovirus attachment protein sigma1 in complex with sialylated oligosaccharides.,Reiter DM, Frierson JM, Halvorson EE, Kobayashi T, Dermody TS, Stehle T PLoS Pathog. 2011 Aug;7(8):e1002166. Epub 2011 Aug 4. PMID:21829363^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.