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.
journal_name
Proc Natl Acad Sci U S Aauthors
Toleman CA,Schumacher MA,Yu SH,Zeng W,Cox NJ,Smith TJ,Soderblom EJ,Wands AM,Kohler JJ,Boyce Mdoi
10.1073/pnas.1722437115subject
Has Abstractpub_date
2018-06-05 00:00:00pages
5956-5961issue
23eissn
0027-8424issn
1091-6490pii
1722437115journal_volume
115pub_type
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