Genetic and molecular analyses reveal an evolutionary trajectory for glycan synthesis in a bacterial protein glycosylation system
Genetic and molecular analyses reveal an evolutionary trajectory for glycan synthesis in a bacterial protein glycosylation system
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DOI：
10.1073/pnas.1103321108
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发表时间：
2011-06-07
影响因子：
11.1
通讯作者：
Koomey, Michael
中科院分区：
文献类型：
--
作者：
Borud, Bente;Viburiene, Raimonda;Koomey, Michael
虽然蛋白质糖基化系统在细菌中得到广泛认可，但对聚糖组成的形成机制和进化力量知之甚少。奈瑟氏菌属内的物种显示出与其O-连接蛋白糖基化（pgl）系统相关的显著糖型变异性，并提供了研究这些现象的良好开发的模型系统。通过研究与核心pgl基因位点相连的两个ORF的潜在影响，我们发现其中一个，以前称为pglH，编码一种葡糖基转移酶，通过使用聚异戊二烯二磷酸连接的单糖底物产生独特的二糖产物。通过定义PglH在糖基化途径中的功能，我们确定了与相对糖基转移酶PglA和PglH之间竞争共享底物相关的代谢冲突。因此，我们提出，淋病奈瑟氏菌、脑膜炎奈瑟氏菌和相关菌株中存在使pglH失活的定型保守缺失突变，反映了这种冲突的解决，其结果是聚糖多样性降低。这种遗传缓和的模型得到了编码蛋白质的pglH“错义”等位基因的表征的支持，所述蛋白质缺乏活性或活性降低，使得它们在PglA存在下不能发挥其作用。因此，含葡萄糖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蛋白质糖基化系统中形成聚糖进化中的作用。
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 glucosyltransferase 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 PglA 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 PglA. 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.