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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Toleman, CA; Schumacher, MA; Yu, S-H; Zeng, W; Cox, NJ; Smith, TJ; Soderblom, EJ; Wands, AM; Kohler, JJ; Boyce, M

Published Date

  • June 5, 2018

Published In

Volume / Issue

  • 115 / 23

Start / End Page

  • 5956 - 5961

PubMed ID

  • 29784830

Pubmed Central ID

  • 29784830

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1722437115


  • eng

Conference Location

  • United States