1. αα-Hub domains and intrinsically disordered proteins: A decisive combo.
- Author
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Bugge K, Staby L, Salladini E, Falbe-Hansen RG, Kragelund BB, and Skriver K
- Subjects
- Animals, Arabidopsis genetics, Arabidopsis metabolism, Arabidopsis Proteins genetics, Arabidopsis Proteins metabolism, Binding Sites, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cytoskeletal Proteins genetics, Cytoskeletal Proteins metabolism, Humans, Intrinsically Disordered Proteins genetics, Intrinsically Disordered Proteins metabolism, Models, Molecular, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Folding, Protein Interaction Domains and Motifs, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Sin3 Histone Deacetylase and Corepressor Complex genetics, Sin3 Histone Deacetylase and Corepressor Complex metabolism, TATA-Binding Protein Associated Factors genetics, TATA-Binding Protein Associated Factors metabolism, Transcription Factor TFIID genetics, Transcription Factor TFIID metabolism, Transcription Factors genetics, Transcription Factors metabolism, Transcription Factors, TFII genetics, Transcription Factors, TFII metabolism, p300-CBP Transcription Factors genetics, p300-CBP Transcription Factors metabolism, Arabidopsis Proteins chemistry, Cell Cycle Proteins chemistry, Cytoskeletal Proteins chemistry, Intrinsically Disordered Proteins chemistry, Sin3 Histone Deacetylase and Corepressor Complex chemistry, TATA-Binding Protein Associated Factors chemistry, Transcription Factor TFIID chemistry, Transcription Factors chemistry, Transcription Factors, TFII chemistry, p300-CBP Transcription Factors chemistry
- Abstract
Hub proteins are central nodes in protein-protein interaction networks with critical importance to all living organisms. Recently, a new group of folded hub domains, the αα-hubs, was defined based on a shared αα-hairpin supersecondary structural foundation. The members PAH, RST, TAFH, NCBD, and HHD are found in large proteins such as Sin3, RCD1, TAF4, CBP, and harmonin, which organize disordered transcriptional regulators and membrane scaffolds in interactomes of importance to human diseases and plant quality. In this review, studies of structures, functions, and complexes across the αα-hubs are described and compared to provide a unified description of the group. This analysis expands the associated molecular concepts of "one domain-one binding site", motif-based ligand binding, and coupled folding and binding of intrinsically disordered ligands to additional concepts of importance to signal fidelity. These include context, motif reversibility, multivalency, complex heterogeneity, synergistic αα-hub:ligand folding, accessory binding sites, and supramodules. We propose that these multifaceted protein-protein interaction properties are made possible by the characteristics of the αα-hub fold, including supersite properties, dynamics, variable topologies, accessory helices, and malleability and abetted by adaptability of the disordered ligands. Critically, these features provide additional filters for specificity. With the presentations of new concepts, this review opens for new research questions addressing properties across the group, which are driven from concepts discovered in studies of the individual members. Combined, the members of the αα-hubs are ideal models for deconvoluting signal fidelity maintained by folded hubs and their interactions with intrinsically disordered ligands., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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