@article{0d40a9ae52dd46a2ba812d462804e01a,
title = "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 unchar-acterized. 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.",
keywords = "14-3-3, EBP1, Enolase, O-GlcNAc, Reader proteins",
author = "Toleman, {Clifford A.} and Schumacher, {Maria A.} and Yu, {Seok Ho} and Wenjie Zeng and Cox, {Nathan J.} and Smith, {Timothy J.} and Soderblom, {Erik J.} and Wands, {Amberlyn M.} and Kohler, {Jennifer J.} and Michael Boyce",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Suzanne Walker (Harvard Medical School) and Pei Zhou (Duke University School of Medicine) for chemicals and plasmids, Benjamin Swarts (Central Michigan University) for Ac45SGlcNAc, the Advanced Light Source beamline 8.3.1 for data collection, and James Alvarez, Jen-Tsan Ashley Chi, Benjamin Swarts, and members of the M.B. laboratory for helpful suggestions. This work was supported by a Rita Allen Foundation Scholar Award and NIH Grants 1R01GM118847-01 and UL1TR001117 (to M.B.), and grants from the NIH (R21DK112733) and Welch Foundation (I-1686) (to J.J.K.). Funding Information: We thank Suzanne Walker (Harvard Medical School) and Pei Zhou (Duke University School of Medicine) for chemicals and plasmids, Benjamin Swarts (Central Michigan University) for Ac45SGlcNAc, the Advanced Light Source beamline 8.3.1 for data collection, and James Alvarez, Jen-Tsan Ashley Chi, Benjamin Swarts, and members of the M.B. laboratory for helpful suggestions. This work was supported by a Rita Allen Foundation Scholar Award and NIH Grants 1R01GM118847-01 and UL1TR001117 (to M.B.), and grants from the NIH (R21DK112733) and Welch Foundation (I-1686) (to J.J.K.). Publisher Copyright: {\textcopyright} 2018 National Academy of Sciences. All Rights Reserved.",
year = "2018",
month = jun,
day = "5",
doi = "10.1073/pnas.1722437115",
language = "English (US)",
volume = "115",
pages = "5956--5961",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "23",
}