Functional glycoproteomics by integrated network assembly and partitioning.

Autor: Griffin ME; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.; Co-first author., Thompson JW; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.; Co-first author., Xiao Y; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.; Co-first author., Sweredoski MJ; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA., Aksenfeld RB; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Jensen EH; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Koldobskaya Y; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Schacht AL; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Kim TD; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Choudhry P; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Lomenick B; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA., Garbis SD; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA., Moradian A; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA., Hsieh-Wilson LC; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.; Lead contact.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 14. Date of Electronic Publication: 2023 Jun 14.
DOI: 10.1101/2023.06.13.541482
Abstrakt: The post-translational modification (PTM) of proteins by O-linked β- N -acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. Here, we describe N etworking of I nteractors and S ubstrat E s (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states.
Competing Interests: DECLARATION OF INTERESTS S.D.G. is founder and CEO/CTO of Proteas Bioanalytics, Inc.
Databáze: MEDLINE