ArticleNucleic acids research2023
Negatively charged, intrinsically disordered regions can accelerate target search by DNA-binding proteins.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- ATRX Condensates as Candidate Organizers of Enhancer-Centered Nuclear Microenvironments in Neural Progenitors: A Hypothesis for Enhancer-Associated ATRX Function in Neural Progenitors.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Counteraction of HMGB1 at ss-dsDNA junctions maintains liquidity of protamine-DNA co-condensates.Nature communications · 2026Article
- APE1 coordinates its disordered region and metal cofactors to drive genome surveillance.Nucleic acids research · 2026Article
- Improving the efficiency of high-fidelity Cas9 by enhancing PAM-distal interactions.Nature structural & molecular biology · 2026Article
- Electrostatic properties of disordered regions control transcription factor search and pioneer activity.Nature communications · 2026Article
- Single-molecule tracking of DNMT1 in living cells reveals its cell cycle dynamics and its redistribution upon drug treatment.Nucleic acids research · 2026Article
- An experimentally-informed polymer model reveals high resolution organization of genomic loci.Nature communications · 2026Article
- HEXIM1 inter-monomer autoinhibition governs 7SK RNA binding specificity and P-TEFb inactivation.Nature communications · 2026Article
- Article
- Challenges in Applying DNA-Binding Protein Predictors to Biological Research.International journal of molecular sciences · 2025Article
- Structure and Mechanism of Aminoacyl-tRNA-Protein L/F- and R-transferases.Journal of molecular biology · 2025Review
- Competition between Nucleic Acids and Intrinsically Disordered Regions within Proteins.Accounts of chemical research · 2025Article
- Phase separated condensates of ATRX regulate neural progenitor identity.Nature communications · 2025Article
- A distinct isoform of Msp300 (nesprin) organizes the perinuclear microtubule-organizing center in adipocytes.Molecular biology of the cell · 2025Article
- Protein and DNA Conformational Changes Contribute to Specificity of Cre Recombinase.Biochemistry · 2025Article
- RNA binding proteins (RBPs) on genetic stability and diseases.Global medical genetics · 2025Review
- Inhibition of HMGA2 binding to AT-rich DNA by its negatively charged C-terminus.Nucleic acids research · 2025Article
- Genome-wide analysis of AP2/ERF transcription Factors inFrontiers in plant science · 2025Article
- How does p53 work? Regulation by the intrinsically disordered domains.Trends in biochemical sciences · 2025Review
- Identification of an Intrinsically Disordered Region (IDR) in Arginyltransferase 1 (ATE1).Biochemistry · 2024Article
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6 authors at 2 institutions in 2 countries.
Funding
Abstract
In eukaryotes, many DNA/RNA-binding proteins possess intrinsically disordered regions (IDRs) with large negative charge, some of which involve a consecutive sequence of aspartate (D) or glutamate (E) residues. We refer to them as D/E repeats. The functional role of D/E repeats is not well understood, though some of them are known to cause autoinhibition through intramolecular electrostatic interaction with functional domains. In this work, we investigated the impacts of D/E repeats on the target DNA search kinetics for the high-mobility group box 1 (HMGB1) protein and the artificial protein constructs of the Antp homeodomain fused with D/E repeats of varied lengths. Our experimental data showed that D/E repeats of particular lengths can accelerate the target association in the overwhelming presence of non-functional high-affinity ligands ('decoys'). Our coarse-grained molecular dynamics (CGMD) simulations showed that the autoinhibited proteins can bind to DNA and transition into the uninhibited complex with DNA through an electrostatically driven induced-fit process. In conjunction with the CGMD simulations, our kinetic model can explain how D/E repeats can accelerate the target association process in the presence of decoys. This study illuminates an unprecedented role of the negatively charged IDRs in the target search process.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.