Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.


O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events remain uncharacterized. One prevalent hypothesis is that O-GlcNAc moieties may be recognized by "reader" proteins to effect downstream signaling. However, no general O-GlcNAc readers have been identified, leaving a considerable gap in the field. To elucidate O-GlcNAc signaling mechanisms, we devised a biochemical screen for candidate O-GlcNAc reader proteins. We identified several human proteins, including 14-3-3 isoforms, that bind O-GlcNAc directly and selectively. We demonstrate that 14-3-3 proteins bind O-GlcNAc moieties in human cells, and we present the structures of 14-3-3β/α and γ bound to glycopeptides, providing biophysical insights into O-GlcNAc-mediated protein-protein interactions. Because 14-3-3 proteins also bind to phospho-serine and phospho-threonine, they may integrate information from O-GlcNAc and O-phosphate signaling pathways to regulate numerous physiological functions.





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Publication Info

Toleman, Clifford A, Maria A Schumacher, Seok-Ho Yu, Wenjie Zeng, Nathan J Cox, Timothy J Smith, Erik J Soderblom, Amberlyn M Wands, et al. (2018). Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins. Proceedings of the National Academy of Sciences of the United States of America, 115(23). pp. 5956–5961. 10.1073/pnas.1722437115 Retrieved from

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Maria Anne Schumacher

Nanaline H. Duke Distinguished Professor of Biochemistry

Erik James Soderblom

Associate Research Professor of Cell Biology

Director, Proteomics and Metabolomics Core Facility


Michael Scott Boyce

Associate Professor of Biochemistry

The Boyce Lab studies mammalian cell signaling through protein glycosylation. For the latest news, project information and publications from our group, please visit our web site at or follow us on Twitter at

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