Structure of a Novel O-Linked N-Acetyl-d-glucosamine (O-GlcNAc) Transferase,GtfA, Reveals Insights into the Glycosylation of Pneumococcal Serine-rich Repeat Adhesins |
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Authors: | Wei-Wei Shi Yong-Liang Jiang Fan Zhu Yi-Hu Yang Qiu-Yan Shao Hong-Bo Yang Yan-Min Ren Hui Wu Yuxing Chen Cong-Zhao Zhou |
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Institution: | From the ‡Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China and ;§Departments of Pediatric Dentistry and Microbiology, University of Alabama at Birmingham, Schools of Dentistry and Medicine, Birmingham, Alabama 35294 |
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Abstract: | Protein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. Here we report the 2.0 Å crystal structure of GtfA, revealing a β-meander add-on domain beyond the catalytic domain. It represents a novel add-on domain, which is distinct from the all-α-tetratricopeptide repeats in the only two structure-known OGTs. Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. |
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Keywords: | Crystal Structure Glycoprotein Biosynthesis Glycosylation Glycosyltransferase Pathogenesis O-GlcNAc Transferase Streptococcus pneumoniae Serine-rich Repeat Glycoprotein |
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