New helical binding domain mediates a glycosyltransferase activity of a bifunctional protein

Hua Zhang, Meixian Zhou, Tiandi Yang, Stuart M. Haslam, Anne Dell, Hui Wu

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Serine-rich repeat glycoproteins (SRRPs) conserved in streptococci and staphylococci are important for bacterial colonization and pathogenesis. Fap1, a well studied SRRP is a major surface constituent of Streptococcus parasanguinis and is required for bacterial adhesion and biofilm formation. Biogenesis of Fap1 is a multistep process that involves both glycosylation and secretion. A series of glycosyltransferases catalyze sequential glycosylation of Fap1. We have identified a unique hybrid protein dGT1 (dual glycosyltransferase 1) that contains two distinct domains. N-terminal DUF1792 is a novel GT-D-type glycosyltransferase, transferring Glc residues to Glc-GlcNAc-modified Fap1. C-terminal dGT1 (CgT) is predicted to possess a typical GT-A-type glycosyltransferase, however, the activity remains unknown. In this study, we determine that CgT is a distinct glycosyltransferase, transferring GlcNAc residues to Glc-Glc-GlcNAc-modified Fap1. A 2.4-Å x-ray crystal structure reveals that CgT has a unique binding domain consisting of three α helices in addition to a typical GT-A-type glycosyltransferase domain. The helical domain is crucial for the oligomerization of CgT. Structural and biochemical studies revealed that the helix domain is required for the protein-protein interaction and crucial for the glycosyltransferase activity of CgT in vitro and in vivo. As the helix domain presents a novel structural fold, we conclude that CgT represents a new member of GT-A-type glycosyltransferases.

Original languageEnglish (US)
Pages (from-to)22106-22117
Number of pages12
JournalJournal of Biological Chemistry
Issue number42
StatePublished - Oct 14 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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