ArticleJournal of molecular biology2019
Residual Structure Accelerates Binding of Intrinsically Disordered ACTR by Promoting Efficient Folding upon Encounter.
Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Coupled Binding and Folding of NS2B/NS3 Protease and Linker Effects Revealed by Topology-Based Modeling.The journal of physical chemistry. B · 2026Article
- Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.Protein science : a publication of the Protein Society · 2026Article
- Coupled Binding and Folding of NS2B/NS3 Protease and Linker Effects Revealed by Topology-based Modeling.bioRxiv : the preprint server for biology · 2026Article
- Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.bioRxiv : the preprint server for biology · 2026Article
- Machine Learning Generation of Dynamic Protein Conformational Ensembles.Molecules (Basel, Switzerland) · 2023Review
- Evolutionary fine-tuning of residual helix structure in disordered proteins manifests in complex structure and lifetime.Communications biology · 2023Article
- Coupled binding and folding of disordered SPIN N-terminal region in myeloperoxidase inhibition.Frontiers in molecular biosciences · 2023Article
- Modeling the Dynamics of Protein-Protein Interfaces, How and Why?Molecules (Basel, Switzerland) · 2022Review
- Investigating Intrinsically Disordered Proteins With Brownian Dynamics.Frontiers in molecular biosciences · 2022Article
- Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions.Biomolecules · 2021Review
- Introducing intrinsic disorder reduces electrostatic steering in protein-protein interactions.Biophysical journal · 2021Article
- Cancer-Associated Mutations Perturb the Disordered Ensemble and Interactions of the Intrinsically Disordered p53 Transactivation Domain.Journal of molecular biology · 2021Article
- Connecting the αα-hubs: same fold, disordered ligands, new functions.Cell communication and signaling : CCS · 2021Article
- Intrinsically Disordered Bacterial Polar Organizing Protein Z, PopZ, Interacts with Protein Binding Partners Through an N-terminal Molecular Recognition Feature.Journal of molecular biology · 2020Article
- Features of molecular recognition of intrinsically disordered proteins via coupled folding and binding.Protein science : a publication of the Protein Society · 2019Review
- Intrinsically Disordered Transactivation Domains Bind to TAZ1 Domain of CBP via Diverse Mechanisms.Biophysical journal · 2019Article
- Investigation into Early Steps of Actin Recognition by the Intrinsically Disordered N-WASP Domain V.International journal of molecular sciences · 2019Article
- Coupled Binding and Helix Formation Monitored by Synchrotron-Radiation Circular Dichroism.Biophysical journal · 2019Article
- Article
- Residual Structures and Transient Long-Range Interactions of p53 Transactivation Domain: Assessment of Explicit Solvent Protein Force Fields.Journal of chemical theory and computation · 2019Article
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3 authors.
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Abstract
Intrinsically disordered proteins (IDPs) often fold into stable structures upon specific binding. The roles of residual structure of unbound IDPs in coupling binding and folding have been under much debate. While many studies emphasize the importance of conformational flexibility for IDP recognition, it was recently demonstrated that stabilization the N-terminal helix of intrinsically disordered ACTR accelerated its binding to another IDP, NCBD of the CREB-binding protein. To understand how enhancing ACTR helicity accelerates binding, we derived a series of topology-based coarse-grained models that mimicked various ACTR mutants with increasing helical contents and reproduced their NCBD binding affinities. Molecular dynamics simulations were then performed to sample hundreds of reversible coupled binding and folding transitions. The results show that increasing ACTR helicity does not alter the baseline mechanism of synergistic folding, which continues to follow "extended conformational selection" with multiple stages of selection and induced folding. Importantly, these coarse-grained models, while only calibrated based on binding thermodynamics, recapitulate the observed kinetic acceleration with increasing ACTR helicity. However, the residual helices do not enhance the association kinetics via more efficient seeding of productive collisions. Instead, they allow the nonspecific collision complexes to evolve more efficiently into the final bound and folded state, which is the primary source of accelerated association kinetics. Meanwhile, reduced dissociation kinetics with increasing ACTR helicity can be directly attributed to smaller entropic cost of forming the bound state. Altogether, this study provides important mechanistic insights into how residual structure may modulate thermodynamics and kinetics of IDP interactions.
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