Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.
| dc.contributor.author | Toleman, Clifford A | |
| dc.contributor.author | Schumacher, Maria A | |
| dc.contributor.author | Yu, Seok-Ho | |
| dc.contributor.author | Zeng, Wenjie | |
| dc.contributor.author | Cox, Nathan J | |
| dc.contributor.author | Smith, Timothy J | |
| dc.contributor.author | Soderblom, Erik J | |
| dc.contributor.author | Wands, Amberlyn M | |
| dc.contributor.author | Kohler, Jennifer J | |
| dc.contributor.author | Boyce, Michael | |
| dc.date.accessioned | 2020-01-01T16:56:16Z | |
| dc.date.available | 2020-01-01T16:56:16Z | |
| dc.date.issued | 2018-06 | |
| dc.date.updated | 2020-01-01T16:56:10Z | |
| dc.description.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. | |
| dc.identifier | 1722437115 | |
| dc.identifier.issn | 0027-8424 | |
| dc.identifier.issn | 1091-6490 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Proceedings of the National Academy of Sciences | |
| dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | |
| dc.relation.isversionof | 10.1073/pnas.1722437115 | |
| dc.subject | Humans | |
| dc.subject | Phosphopyruvate Hydratase | |
| dc.subject | Acetylglucosamine | |
| dc.subject | 14-3-3 Proteins | |
| dc.subject | Proteomics | |
| dc.subject | Models, Molecular | |
| dc.subject | Mass Spectrometry | |
| dc.subject | HEK293 Cells | |
| dc.title | Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Boyce, Michael|0000-0002-2729-4876 | |
| pubs.begin-page | 5956 | |
| pubs.end-page | 5961 | |
| pubs.issue | 23 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Biochemistry | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Cell Biology | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Student | |
| pubs.organisational-group | Molecular Genetics and Microbiology | |
| pubs.publication-status | Published | |
| pubs.volume | 115 |
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