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

Abstract

Significance O-GlcNAc is an abundant, reversible posttranslational modification (PTM) of nuclear and cytoplasmic proteins in animals and plants. O-GlcNAc regulates a wide range of biological processes, and aberrant O-GlcNAcylation is implicated in numerous human diseases. However, key aspects of O-GlcNAc signaling remain poorly understood. For example, it is not known whether “reader” proteins exist to recognize and bind to O-GlcNAc, as is true for many other PTMs. We used a biochemical method to identify candidate human O-GlcNAc reader proteins, and then characterized them at the biochemical and biophysical levels. Our results address a significant gap in the cell signaling field by revealing the biochemical and structural basis for the recognition of O-GlcNAc by conserved human proteins.