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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genetic and molecular analyses reveal an evolutionary trajectory for glycan synthesis in a bacterial protein glycosylation system
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Genetic and molecular analyses reveal an evolutionary trajectory for glycan synthesis in a bacterial protein glycosylation system

机译:遗传和分子分析揭示了细菌蛋白质糖基化系统中聚糖合成的进化轨迹。

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摘要

Although protein glycosylation systems are becoming widely recognized in bacteria, little is known about the mechanisms and evolutionary forces shaping glycan composition. Species within the genus Neisseria display remarkable glycoform variability associated with their O-linked protein glycosylation (pgl) systems and provide a well developed model system to study these phenomena. By examining the potential influence of two ORFs linked to the core pgl gene locus, we discovered that one of these, previously designated as pglH. encodes a glucosyrtransferase that generates unique disaccharide products by using polyprenyl diphosphate-linked monosaccharide substrates. By defining the function of PglH in the glycosylation pathway, we identified a metabolic conflict related to competition for a shared substrate between the opposing glycosyltransferases PgIA and PglH. Accordingly, we propose that the presence of a stereotypic, conserved deletion mutation inactivating pglH in strains of Neisseria gonorrhoeae, Neisseria meningitidis. and related commensals, reflects a resolution of this conflict with the consequence of reduced glycan diversity. This model of genetic detente is supported by the characterization of pglH "missense" alleles encoding proteins devoid of activity or reduced in activity such that they cannot exert their effect in the presence of PgIA. Thus, glucose-containing glycans appear to be a trait undergoing regression at the genus level. Together, these findings document a role for intrinsic genetic interactions in shaping glycan evolution in protein glycosylation systems.
机译:尽管蛋白质糖基化系统已在细菌中得到广泛认可,但对形成聚糖成分的机制和进化力知之甚少。奈瑟氏球菌属中的物种显示出与它们的O联蛋白糖基化(pgl)系统相关的显着糖型变异性,并为研究这些现象提供了完善的模型系统。通过检查链接到核心pgl基因位点的两个ORF的潜在影响,我们发现其中一个以前称为pglH。编码通过使用聚异戊二烯二磷酸连接的单糖底物生成独特的二糖产物的葡糖基转移酶。通过定义PglH在糖基化途径中的功能,我们确定了与相对的糖基转移酶PgIA和PglH之间共享底物竞争有关的代谢冲突。因此,我们提出在淋病奈瑟氏球菌,脑膜炎奈瑟氏球菌的菌株中存在定型的,保守的缺失突变使pglH失活。以及相关的推荐,反映了这种冲突的解决,其聚糖多样性降低。 pglH“缺失”等位基因的表征支持了这种遗传性缓和模型,该等位基因编码的蛋白缺乏活性或活性降低,因此在存在PgIA时它们无法发挥作用。因此,含葡萄糖的聚糖似乎是在属水平上经历退化的性状。总之,这些发现证明了内在遗传相互作用在塑造蛋白质糖基化系统中的聚糖进化中的作用。

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  • 作者单位

    Center for Molecular Biology and Neuroscience and Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway;

    Center for Molecular Biology and Neuroscience and Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway;

    Departments of Chemistry and Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;

    Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo,0316 Oslo, Norway;

    Center for Molecular Biology and Neuroscience and Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway,Glyconor Mass Spectrometry and Proteomics Unit, University of Oslo, 0316 Oslo, Norway;

    Departments of Chemistry and Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;

    Center for Molecular Biology and Neuroscience and Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway;

  • 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

    epistasis; oligosaccharide biosynthesis; type IV pili;

    机译:上位性寡糖生物合成;IV型菌毛;

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