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Updated: May 17, 2025

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Intrinsically Disordered Regions Define Unique Protein Interaction Networks in CHD Family Remodelers
Mehdi Sharifi Tabar1,2,3, Chirag Parsania1,2,3, Caroline Giardina2
1Faculty of Medicine & Health, The University of Sydney, Camperdown, New South Wales, Australia.
Abstract:
Chromodomain helicase DNA-binding (CHD) enzymes play a pivotal role in genome regulation. They possess highly conserved ATPase domains flanked by poorly characterized and intrinsically disordered N- and C-termini. Using mass spectrometry, we identify dozens of novel protein-protein interactions (PPIs) within the N- and C-termini of human CHD family members. We also define a highly conserved aggregation-prone region (APR) within the C-terminus of CHD4 which is critical for its interaction with the nucleosome remodeling and deacetylase (NuRD), as well as ChAHP (CHD4, activity-dependent neuroprotective protein (ADNP), and HP1γ) complexes. Further analysis reveals a regulatory role for the CHD4 APR in gene transcription during erythrocyte formation. Our results highlight that the N- and C-termini of CHD chromatin remodelers shape protein interaction networks that drive unique transcriptional programs.
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