Emerging structural insights into C-type glycosyltransferases

Glycosyltransferases of the C superfamily (GT-Cs) are enzymes found in all domains of life. They catalyse the stepwise synthesis of oligosaccharides or the transfer of assembled glycans from lipid-linked donor substrates to acceptor proteins. The processes mediated by GT-Cs are required for C-, N- and O-linked glycosylation, all of which are essential post-translational modifications in higher-order eukaryotes. Until recently, GT-Cs were thought to share a conserved structural module of 7 transmembrane helices; however, recently determined GT-C structures revealed novel folds. Here we analyse the growing diversity of GT-C folds and discuss the emergence of two subclasses, termed GT-C_A and GT-C_B. Further substrate-bound structures are needed to facilitate a molecular understanding of glycan recognition and catalysis in these two subclasses.