Novel aspects of sialoglycan recognition by the Siglec-like domains of streptococcal SRR glycoproteins
Novel aspects of sialoglycan recognition by the Siglec-like domains of streptococcal SRR glycoproteins
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DOI：
10.1093/glycob/cww042
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发表时间：
2016-11-01
期刊：
影响因子：
4.3
通讯作者：
Sullam, Paul M.
中科院分区：
文献类型：
--
作者：
Bensing, Barbara A.;Khedri, Zahra;Sullam, Paul M.
富含丝氨酸的重复糖蛋白是由细菌和致病性革兰氏阳性菌表达的粘附素。由口腔链球菌表达的这些粘附素的一个子集结合修饰人唾液粘蛋白MG 2/MUC 7和血小板糖蛋白GPIb的唾液酸化聚糖。特异性唾液酸聚糖靶点先前被鉴定为GspB和Hsa的配体结合区（BR），这两种富含丝氨酸的重复糖蛋白由戈登链球菌表达。虽然GspB选择性结合唾液酸-T抗原，但Hsa显示更广泛的特异性。在这里，我们研究了四个额外的BR从血链球菌或缓症链球菌的结合特性，并表征配体的选择性和亲和力的分子决定因素。每个BR具有两个结构域，这两个结构域对于GspB结合唾液酸聚糖是必需的。一个结构域在结构上类似于哺乳动物Siglecs（唾液酸结合免疫球蛋白样凝集素）的聚糖结合模块，包括对聚糖识别至关重要的精氨酸残基，并且位于新的保守YTRY基序内。尽管与GspB的序列相似性较低，但其中一种BR选择性地结合唾液酸-T抗原。尽管其他三种BR与Hsa高度相似，但每种BR都显示出独特的配体库，包括对唾液酸刘易斯抗原和硫酸化聚糖的差异识别。聚糖选择性的这些差异与唾液和血小板糖蛋白的差异结合密切相关。唾液酸聚糖粘附的特异性可能是一种不断发展的特征，可能会影响表达Siglec样粘附素的链球菌引起感染性心内膜炎的倾向。
Serine-rich repeat glycoproteins are adhesins expressed by commensal and pathogenic Gram-positive bacteria. A subset of these adhesins, expressed by oral streptococci, binds sialylated glycans decorating human salivary mucin MG2/MUC7, and platelet glycoprotein GPIb. Specific sialoglycan targets were previously identified for the ligand-binding regions (BRs) of GspB and Hsa, two serine-rich repeat glycoproteins expressed by Streptococcus gordonii. While GspB selectively binds sialyl-T antigen, Hsa displays broader specificity. Here we examine the binding properties of four additional BRs from Streptococcus sanguinis or Streptococcus mitis and characterize the molecular determinants of ligand selectivity and affinity. Each BR has two domains that are essential for sialoglycan binding by GspB. One domain is structurally similar to the glycan-binding module of mammalian Siglecs (sialic acid-binding immunoglobulin-like lectins), including an arginine residue that is critical for glycan recognition, and that resides within a novel, conserved YTRY motif. Despite low sequence similarity to GspB, one of the BRs selectively binds sialyl-T antigen. Although the other three BRs are highly similar to Hsa, each displayed a unique ligand repertoire, including differential recognition of sialyl Lewis antigens and sulfated glycans. These differences in glycan selectivity were closely associated with differential binding to salivary and platelet glycoproteins. Specificity of sialoglycan adherence is likely an evolving trait that may influence the propensity of streptococci expressing Siglec-like adhesins to cause infective endocarditis.