Polypeptide GalNAc-Ts: from redundancy to specificity

被引:82
作者
de las Rivas, Matilde [1 ]
Lira-Navarrete, Erandi [2 ]
Gerken, Thomas A. [3 ,4 ,5 ]
Hurtado-Guerrero, Ramon [1 ,6 ]
机构
[1] Univ Zaragoza, BIFI, BIFI IQFR CSIC Joint Unit, Mariano Esquillor S-N,Campus Rio Ebro,Edificio ID, Zaragoza, Spain
[2] Univ Copenhagen, Copenhagen Ctr Glyc, Sch Dent, Dept Cellular & Mol Med, Copenhagen, Denmark
[3] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA
[4] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA
[5] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA
[6] Fdn ARAID, Zaragoza 50018, Spain
基金
美国国家卫生研究院;
关键词
O-GLYCOSYLATION; LECTIN DOMAINS; UDP-GALNAC; CATALYTIC-DOMAIN; GLYCOSYLTRANSFERASES; CANCER; SITE; FAMILY; MUCINS;
D O I
10.1016/j.sbi.2018.12.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:87 / 96
页数:10
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