6BYJ

Structure of human 14-3-3 gamma bound to O-GlcNAc peptide

Summary for 6BYJ

• Entry DOI: 10.2210/pdb6byj/pdb
• Descriptor: 14-3-3 protein gamma, TSTTATPPVSQASSTTTSTW O-GlcNac peptide, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: 14-3-3 gamma, o-glcnac, signalling, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 9
• Total formula weight: 172761.41

Authors

Schumacher, M.A. (deposition date: 2017-12-20, release date: 2018-05-09, Last modification date: 2024-11-06)

Primary citation

Toleman, C.A.,Schumacher, M.A.,Yu, S.H.,Zeng, W.,Cox, N.J.,Smith, T.J.,Soderblom, E.J.,Wands, A.M.,Kohler, J.J.,Boyce, M.
Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.
Proc.Natl.Acad.Sci.USA, 115:5956-5961, 2018

PubMed 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.

PubMed: 29784830
DOI: 10.1073/pnas.1722437115

Experimental method

X-RAY DIFFRACTION (2.9 Å)