22 research outputs found

    Crystal Structure of Reovirus Attachment Protein σ1 in Complex with Sialylated Oligosaccharides

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    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 σ1 in complex with α-2,3-sialyllactose, α-2,6-sialyllactose, and α-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 σ1 resembles an elongated, filamentous trimer. It contains a globular head featuring a compact ÎČ-barrel, and a fibrous extension formed by seven repeating units of a triple ÎČ-spiral that is interrupted near its midpoint by a short α -helical coiled coil. The carbohydrate-binding site is located between ÎČ-spiral repeats two and three, distal from the head. In all three complexes, the terminal sialic acid forms almost all of the contacts with σ1 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 σ1 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 σ1 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

    ICAR: endoscopic skull‐base surgery

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    Risk and resilience in gifted young people from low socio-economic backgrounds

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    Gifted and talented young people from low socio-economic backgrounds are consistently under-represented in gifted programmes in New Zealand schools. This chapter reports on a qualitative study that explored the lived experiences of 101 gifted New Zealand young people from low socio-economic back-grounds. An overarching question for this study was ‘What is it about gifted young people from low socio-economic backgrounds who have achieved to exceptional levels, that has enabled them to do so?’ The risk and resilience construct was used as a lens through which to explore their experiences across a range of contexts. These young people reflected on their perceptions of their giftedness and socio-economic circumstances, their childhoods and school ex-periences, and their home lives. The stories of the participants in this study in-dicated that there are particular risks associated with both giftedness and low socio-economic status, and contribute to ideas about how these young people might be more effectively supported to develop their potential
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