Zhou Guo-Ping, Huang Ri-Bo, Troy Frederic A
National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi 530007, China.
Protein Pept Lett. 2015;22(2):137-48. doi: 10.2174/0929866521666141019192221.
Synthesis of α2,8-polysialic acid (polySia) glycans are catalyzed by two highly homologous mammalian polysialyltransferases (polySTs), ST8Sia II (STX) and ST8Sia IV (PST), which are two members of the ST8Sia gene family of sialytransferases. During polysialylation, both STX and PST catalyze the transfer of multiple Sia residues from the activated sugar nucleotide precursor, CMP-Neu5Ac (Sia), to terminal Sia residues on N- and Olinked oligosaccharide chains on acceptor glycoproteins, including the neural cell adhesion molecule (NCAM), which is the major carrier protein of polySia. Based on our new findings and previously published studies, this review summarizes the present concepts regarding the molecular mechanism underlying regulation of protein-specific polysialylation of NCAM that includes the following: (1) Determination of the catalytic domains and specific regions within ST8Sia IV for recognizing and catalyzing the efficient polysialylation of NCAM; (2) Identification of key amino acid residues within the PSTD motif of ST8Sia IV that are essential for polysialylation; (3) Verification of key amino acids in the PBR domain of ST8Sia IV required for NCAM-specific polysialylation; and (4) a 3D conformational study of ST8Sia IV based on the Phyre2 server to discover the relationship between the structure and its functional domains of the polyST. Based on these results, our 3D model of ST8Sia IV was used to identify and characterize the catalytic domains and amino acid residues critical for catalyzing polysialylation, and have provided new structural information for supporting a detailed mechanism of polyST-NCAM interaction required for polysialylation of NCAM, findings that have not been previously reported.
α2,8-聚唾液酸（polySia）聚糖的合成由两种高度同源的哺乳动物多唾液酸转移酶（polySTs）催化，即ST8Sia II（STX）和ST8Sia IV（PST），它们是唾液酸转移酶ST8Sia基因家族的两个成员。在多唾液酸化过程中，STX和PST都催化多个唾液酸残基从活化的糖核苷酸前体CMP-神经氨酸（Sia）转移到受体糖蛋白上N-连接和O-连接寡糖链的末端唾液酸残基上，其中包括神经细胞黏附分子（NCAM），它是polySia的主要载体蛋白。基于我们的新发现和先前发表的研究，本综述总结了目前关于NCAM蛋白质特异性多唾液酸化调控的分子机制的概念，包括以下内容：（1）确定ST8Sia IV中用于识别和催化NCAM有效多唾液酸化的催化结构域和特定区域；（2）鉴定ST8Sia IV的PSTD基序中对多唾液酸化至关重要的关键氨基酸残基；（3）验证ST8Sia IV的PBR结构域中NCAM特异性多唾液酸化所需的关键氨基酸；（4）基于Phyre2服务器对ST8Sia IV进行三维构象研究，以发现多唾液酸转移酶的结构与其功能结构域之间的关系。基于这些结果，我们构建的ST8Sia IV三维模型用于识别和表征催化多唾液酸化至关重要的催化结构域和氨基酸残基，并为支持NCAM多唾液酸化所需的多唾液酸转移酶-NCAM相互作用的详细机制提供了新的结构信息，这些发现以前尚未见报道。
