ArticleJournal of molecular biology2021
Dynamic Autoinhibition of the HMGB1 Protein via Electrostatic Fuzzy Interactions of Intrinsically Disordered Regions.
Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- HMGB1 as a danger signal in vascular remodeling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Review
- Fractional Ion Contributions to Mixed Electrolyte Ion Atmospheres from Experimental Thermodynamic Data.The journal of physical chemistry. B · 2026Article
- Revealing the Biological Effect of theJournal of the American Chemical Society · 2026Article
- Ion Adsorption at Surfaces from Local and Global Electroneutrality Constraints.Langmuir : the ACS journal of surfaces and colloids · 2026Article
- HMGB1 as an emerging key modulator of bone remodeling: a narrative review.Stem cell research & therapy · 2025Review
- Competition between Nucleic Acids and Intrinsically Disordered Regions within Proteins.Accounts of chemical research · 2025Article
- Extreme multivalency and a composite short linear motif facilitate PCNA-binding, localisation and abundance of p21 (CDKN1A).The FEBS journal · 2025Article
- Intrinsically disordered regions as facilitators of the transcription factor target search.Nature reviews. Genetics · 2025Review
- Role of charges in a dynamic disordered complex between an IDP and a folded domain.Nature communications · 2025Article
- Protein and DNA Conformational Changes Contribute to Specificity of Cre Recombinase.Biochemistry · 2025Article
- Protein and DNA Conformational Changes Contribute to Specificity of Cre Recombinase.bioRxiv : the preprint server for biology · 2024Article
- Fuzzy protein-DNA interactions and beyond: A common theme in transcription?Current opinion in structural biology · 2024Review
- Phosphorylation by Protein Kinase C Weakens DNA-Binding Affinity and Folding Stability of the HMGB1 Protein.Biochemistry · 2024Article
- Skipping events impose repeated binding attempts: profound kinetic implications of protein-DNA conformational changes.Nucleic acids research · 2024Article
- Influence of an Intrinsically Disordered Region on Protein Domains Revealed by NMR-Based Electrostatic Potential Measurements.Journal of the American Chemical Society · 2024Article
- Conserved molecular recognition by an intrinsically disordered region in the absence of sequence conservation.Research square · 2024Article
- The multifunctional protein HMGB1: 50 years of discovery.Nature reviews. Immunology · 2023Review
- Direct measurements of biomolecular electrostatics through experiments.Current opinion in structural biology · 2023Review
- Negatively charged, intrinsically disordered regions can accelerate target search by DNA-binding proteins.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Highly negatively charged segments containing only aspartate or glutamate residues ("D/E repeats") are found in many eukaryotic proteins. For example, the C-terminal 30 residues of the HMGB1 protein are entirely D/E repeats. Using nuclear magnetic resonance (NMR), fluorescence, and computational approaches, we investigated how the D/E repeats causes the autoinhibition of HMGB1 against its specific binding to cisplatin-modified DNA. By varying ionic strength in a wide range (40-900 mM), we were able to shift the conformational equilibrium between the autoinhibited and uninhibited states toward either of them to the full extent. This allowed us to determine the macroscopic and microscopic equilibrium constants for the HMGB1 autoinhibition at various ionic strengths. At a macroscopic level, a model involving the autoinhibited and uninhibited states can explain the salt concentration-dependent binding affinity data. Our data at a microscopic level show that the D/E repeats and other parts of HMGB1 undergo electrostatic fuzzy interactions, each of which is weaker than expected from the macroscopic autoinhibitory effect. This discrepancy suggests that the multivalent nature of the fuzzy interactions enables strong autoinhibition at a macroscopic level despite the relatively weak intramolecular interaction at each site. Both experimental and computational data suggest that the D/E repeats interact preferentially with other intrinsically disordered regions (IDRs) of HMGB1. We also found that mutations mimicking post-translational modifications relevant to nuclear export of HMGB1 can moderately modulate DNA-binding affinity, possibly by impacting the autoinhibition. This study illuminates a functional role of the fuzzy interactions of D/E repeats.
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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.