Polypeptide GalNAc-Ts: from redundancy to specificity
Polypeptide GalNAc-Ts: from redundancy to specificity
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DOI：
10.1016/j.sbi.2018.12.007
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发表时间：
2019-06-01
影响因子：
6.8
通讯作者：
Hurtado-Guerrero, Ramon
中科院分区：
文献类型：
--
作者：
de las Rivas, Matilde;Lira-Navarrete, Erandi;Hurtado-Guerrero, Ramon
粘蛋白型 O-糖基化是一种翻译后修饰 (PTM)，预计 80% 以上通过高尔基体的蛋白质都会发生这种修饰。该 PTM 由多肽 GalNAc 转移酶 (GalNAc-Ts) 家族启动，该家族通过添加 GalNAc 部分来修饰蛋白质的 Ser 和 Thr 残基。这些酶是 II 型膜蛋白，由通过柔性接头连接到蓖麻毒素型凝集素结构域的高尔基体腔催化结构域组成。两个结构域共同解释了同工酶中观察到的不同糖基化偏好。尽管人们普遍认为大多数家族成员对其蛋白质和糖蛋白底物具有一定程度的冗余，但最近发现一些 GalNAc-T 也具有针对特定靶标的活性。尽管同工酶之间高度相似，但最近报道的结构差异对于理解其冗余性和特异性的分子基础至关重要。本综述重点关注蛋白质底物识别的分子方面以及这些酶的不同糖基化偏好，这反过来将作为粘蛋白型 O-糖基化特定调节剂的合理设计的路线图。
Mucin-type O-glycosylation is a post-translational modification (PTM) that is predicted to occur in more than the 80% of the proteins that pass through the Golgi apparatus. This PTM is initiated by a family of polypeptide GalNAc-transferases (GalNAc-Ts) that modify Ser and Thr residues of proteins through the addition of a GalNAc moiety. These enzymes are type II membrane proteins that consist of a Golgi luminal catalytic domain connected by a flexible linker to a ricin type lectin domain. Together, both domains account for the different glycosylation preferences observed among isoenzymes. Although it is well accepted that most of the family members share some degree of redundancy toward their protein and glycoprotein substrates, it has been recently found that several GalNAc-Ts also possess activity toward specific targets. Despite the high similarity between isoenzymes, structural differences have recently been reported that are key to understanding the molecular basis of both their redundancy and specificity. The present review focuses on the molecular aspects of the protein substrate recognition and the different glycosylation preferences of these enzymes, which in turn will serve as a roadmap to the rational design of specific modulators of mucin-type O-glycosylation.