Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.
Abstract
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.
Type
Journal articleSubject
HumansPhosphopyruvate Hydratase
Acetylglucosamine
14-3-3 Proteins
Proteomics
Models, Molecular
Mass Spectrometry
HEK293 Cells
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https://hdl.handle.net/10161/19689Published Version (Please cite this version)
10.1073/pnas.1722437115Publication Info
Toleman, Clifford A; Schumacher, Maria A; Yu, Seok-Ho; Zeng, Wenjie; Cox, Nathan J;
Smith, Timothy J; ... Boyce, Michael (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 https://hdl.handle.net/10161/19689.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
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 http://www.boycelab.org or follow us on Twitter at https://twitter.com/BoyceLab.
Maria Anne Schumacher
Nanaline H. Duke Distinguished Professor of Biochemistry
Tim Smith
Student
Erik James Soderblom
Associate Research Professor of Cell Biology
Director, Proteomics and Metabolomics Core Facility
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