Title : Exploring the O-GlcNAc proteome: direct identification of O-GlcNAc-modified proteins from the brain
Abstract :
- The covalent modification of intracellular proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) is emerging as a crucial regulatory posttranslational modification akin to phosphorylation
- Numerous studies point to the significance of O-GlcNAc in cellular processes such as nutrient sensing, protein degradation, and gene expression
- Despite its importance, the breadth and functional roles of O-GlcNAc are only beginning to be elucidated
- Advances in our understanding will require the development of new strategies for the detection and study of O-GlcNAc-modified proteins in vivo
- Herein we report the direct, high-throughput analysis of O-GlcNAc-glycosylated proteins from the mammalian brain
- The proteins were identified by using a chemoenzymatic approach that exploits an engineered galactosyltransferase enzyme to selectively label O-GlcNAc proteins with a ketone-biotin tag
- The tag permits enrichment of low-abundance O-GlcNAc species from complex mixtures and localization of the modification to short amino acid sequences
- Using this approach, we discovered 25 O-GlcNAc-glycosylated proteins from the brain, including regulatory proteins associated with gene expression, neuronal signaling, and synaptic plasticity
- The functional diversity represented by this set of proteins suggests an expanded role for O-GlcNAc in regulating neuronal function
- Moreover, the chemoenzymatic strategy described here should prove valuable for identifying O-GlcNAc-modified proteins in various tissues and facilitate studies of the physiological significance of O-GlcNAc across the proteome
Output (sent_index, trigger,
protein,
sugar,
site):
- 5. O-GlcNAc-glycosylated, , -, O-GlcNAc-glycosylated proteins, -
- 8. O-GlcNAc-glycosylated, , proteins, 25 O-GlcNAc-glycosylated proteins, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
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