期刊
CURRENT OPINION IN STRUCTURAL BIOLOGY
卷 44, 期 -, 页码 219-231出版社
CURRENT BIOLOGY LTD
DOI: 10.1016/j.sbi.2017.06.001
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资金
- NCI NIH HHS [U01 CA207824] Funding Source: Medline
- NIGMS NIH HHS [P41 GM103390] Funding Source: Medline
Understanding the molecular origin of influenza receptor specificity is complicated by the paucity of quantitative affinity measurements, and the qualitative and variable nature of glycan array data. Further obstacles arise from the varied impact of viral glycosylation and the relatively narrow spectrum of biologically relevant receptors present on glycan arrays. A survey of receptor conformational properties is presented, leading to the conclusion that conformational entropy plays a key role in defining specificity, as does the newly reported ability of biantennary receptors that terminate in Siaa2-6Gal sequences to form bidentate interactions to two binding sites in a hemagglutinin trimer. Bidentate binding provides a functional explanation for the observation that Siaa2-6 receptors adopt an open-umbrella topology when bound to hemagglutinins from human-infective viruses, and calls for a reassessment of virus avidity and tissue tropism.Understanding the molecular origin of influenza receptor specificity is complicated by the paucity of quantitative affinity measurements, and the qualitative and variable nature of glycan array data. Further obstacles arise from the varied impact of viral glycosylation and the relatively narrow spectrum of biologically relevant receptors present on glycan arrays. A survey of receptor conformational properties is presented, leading to the conclusion that conformational entropy plays a key role in defining specificity, as does the newly reported ability of biantennary receptors that terminate in Siaa2-6Gal sequences to form bidentate interactions to two binding sites in a hemagglutinin trimer. Bidentate binding provides a functional explanation for the observation that Siaa2-6 receptors adopt an open-umbrella topology when bound to hemagglutinins from human-infective viruses, and calls for a reassessment of virus avidity and tissue tropism.
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