PRISMA: Protein Interaction Screen on Peptide Matrix reveals interaction footprints and modifications- dependent interactome of intrinsically disordered C/EBPb

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Item Type:

Article

Title:

PRISMA: Protein Interaction Screen on Peptide Matrix reveals interaction footprints and modifications- dependent interactome of intrinsically disordered C/EBPb

Creators Name:

Dittmar, G. and Perez Hernandez, D. and Kowenz-Leutz, E. and Kirchner, M. and Kahlert, G. and Wesolowski, R. and Baum, K. and Knoblich, M. and Hofstätter, M. and Muller, A. and Wolf, J. and Reimer, U. and Leutz, A.

Abstract:

CCAAT enhancer binding protein beta (C/EBPβ) is a pioneer transcription factor that specifies cell differentiation. C/EBPβ is intrinsically unstructured, a molecular feature common to many proteins involved in signal processing and epigenetics. The structure of C/EBPβ differs depending on alternative translation initiation and multiple post-translational modifications (PTM). Mutation of distinct PTM sites in C/EBPβ alters protein interactions and cell differentiation, suggesting a C/EBPβ PTM indexing code determines epigenetic outcomes. Herein, we systematically explored the interactome of C/EBPβ using an array technique based on spot-synthesized C/EBPβ-derived linear tiling peptides with and without PTM, combined with mass spectrometric proteomic analysis of protein interactions (PRISMA). We identified interaction footprints of ∼1300 proteins in nuclear extracts, many with chromatin modifying, remodeling and RNA processing functions. The results suggest C/EBPβ acts as a multi-tasking molecular switchboard, integrating signal-dependent modifications and structural plasticity to orchestrate interactions with numerous protein complexes directing cell fate and function.

Keywords:

C/EBPβ, PRISMA, Intrinsically Disordered Protein, Post-Translational Modification, Mass Spectrometry

Source:

iScience

ISSN:

2589-0042

Publisher:

Cell Press

Volume:

Page Range:

351-370

Date: