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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural basis for ligand and substrate recognition by torovirus hemagglutinin esterases
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Structural basis for ligand and substrate recognition by torovirus hemagglutinin esterases

机译：环状病毒血凝素酯酶识别配体和底物的结构基础

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摘要

Hemagglutinin esterases (HEs), closely related envelope glycopro-teins in influenza C and corona- and toroviruses, mediate reversible attachment to O-acetylated sialic acids (Sias). They do so by acting both as lectins and as receptor-destroying enzymes, functions exerted by separate protein domains. HE divergence was accompanied by changes in quaternary structure and in receptor and substrate specificity. The selective forces underlying HE diversity and the molecular basis for Sia specificity are poorly understood. Here we present crystal structures of porcine and bovine torovirus HEs in complex with receptor analogs. Torovirus HEs form homodimers with sialate-O-acetylesterase domains almost identical to corresponding domains in orthomyxo- and coronavirus HEs, but with unique lectin sites. Structure-guided biochemical analysis of the esterase domains revealed that a functionally, but not structurally conserved arginine-Sia car-boxylate interaction is critical for the binding and positioning of glycosidically bound Sias in the catalytic pocket. Although essential for efficient de-O-acetylation of Sias, this interaction is not required for catalysis nor does it affect substrate specificity. In fact, the distinct preference of the porcine torovirus enzyme for 9-mono- over 7,9-di-O-acetylated Sias can be explained from a single-residue difference with HEs of more promiscuous specificity. Apparently, esterase and lectin pockets coevolved; also the porcine torovirus HE receptor-binding site seems to have been designed to use 9-mono- and exclude di-O-acetylated Sias, possibly as an adaptation to replication in swine. Our findings shed light on HE evolution and provide fundamental insight into mechanisms of substrate binding, substrate recognition, and receptor selection in this important class of virion proteins.
机译：血凝素酯酶（HEs），与丙型流感，冠状病毒和轮状病毒密切相关的包膜糖蛋白，介导与O-乙酰化唾液酸（Sias）的可逆连接。它们通过充当凝集素和破坏受体的酶来实现，这是由单独的蛋白质结构域发挥的功能。 HE的发散伴随着四级结构以及受体和底物特异性的变化。对HE多样性和Sia特异性的分子基础的选择力了解甚少。在这里，我们介绍了与受体类似物复合的猪和牛轮状病毒HE的晶体结构。轮状病毒HE形成的同源二聚体具有唾液酸-O-乙酰酯酶结构域，该结构与正粘病毒和冠状病毒HE中的相应结构域几乎相同，但具有独特的凝集素位点。对酯酶结构域进行结构指导的生化分析表明，功能上但非结构上保守的精氨酸-Sia羧酸盐相互作用对于糖苷键结合的Sias在催化口袋中的结合和定位至关重要。尽管对于Sias的高效去O-乙酰化必不可少，但这种相互作用不是催化所必需的，也不影响底物特异性。实际上，猪轮状病毒酶对9-单-，7,9-二-O-乙酰化的Sias的独特偏好可以从具有更高混杂特异性的HE的单残基差异来解释。显然，酯酶和凝集素的口袋共同进化。猪轮状病毒HE受体结合位点似乎也被设计为使用9-单-和排除双-O-乙酰化的Sias，可能是为了适应猪中的复制。我们的发现阐明了HE的进化，并提供了对这一重要病毒粒子蛋白中底物结合，底物识别和受体选择机制的基本见解。

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  • 作者

    Martijn A. Langereis; Qinghong Zeng; Gerrit J. Gerwig; Barbara Frey; Mark von ltzstein; Johannis P. Kamerling; Raoul J. de Groot; Eric G. Huizinga;

  • 作者单位

    Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine;

    Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Sciences;

    Department of Bio-Organic Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands;

    lnstitute for Glycomics, Gold Coast Campus, Griffith University, Queensland, 4222, Australia;

    lnstitute for Glycomics, Gold Coast Campus, Griffith University, Queensland, 4222, Australia;

    Department of Bio-Organic Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands;

    Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine;

    Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Sciences;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    glycobiology; influenza; nidovirus; sialate-O-acetylesterase; X-ray crystallography;

    机译：糖生物学流感;病毒唾液酸-O-乙酰酯酶;X射线晶体学;

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