ArticleProceedings of the National Academy of Sciences of the United States of America2014
Interplay between partner and ligand facilitates the folding and binding of an intrinsically disordered protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed.
- Alternative Splicing of a Structured Partner Alters the Folding-Upon-Binding Trajectory of an Intrinsically Disordered Protein.Journal of the American Chemical Society · 2026Article
- Sequence-encoded conformational biases correlate with self-assembly modes of intrinsically disordered proteins.PNAS nexus · 2026Article
- Navigating protein landscapes with a machine-learned transferable coarse-grained model.Nature chemistry · 2025Article
- Hierarchy in regulator interactions with distant transcriptional activation domains empowers rheostatic regulation.Protein science : a publication of the Protein Society · 2025Article
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- The transition state for coupled folding and binding of a disordered DNA binding domain resembles the unbound state.Nucleic acids research · 2024Article
- CD28 hinge used in chimeric antigen receptor (CAR) T-cells exhibits local structure and conformational exchange amidst global disorder.Communications biology · 2024Article
- The molecular basis for cellular function of intrinsically disordered protein regions.Nature reviews. Molecular cell biology · 2024Review
- Folding-upon-binding pathways of an intrinsically disordered protein from a deep Markov state model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural biases in disordered proteins are prevalent in the cell.Nature structural & molecular biology · 2024Article
- Intrinsically disordered regions are poised to act as sensors of cellular chemistry.Trends in biochemical sciences · 2023Review
- Phase Transitions of Associative Biomacromolecules.Chemical reviews · 2023Review
- Folding-upon-binding pathways of an intrinsically disordered protein from a deep Markov state model.bioRxiv : the preprint server for biology · 2023Article
- Functional regulation of an intrinsically disordered protein via a conformationally excited state.Science advances · 2023Article
- Targeting Protein-Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches.International journal of molecular sciences · 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
- A modular approach to map out the conformational landscapes of unbound intrinsically disordered proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- NMR Provides Unique Insight into the Functional Dynamics and Interactions of Intrinsically Disordered Proteins.Chemical reviews · 2022Review
21 more citing papers are in PubMed but not listed here.
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7 authors.
Funding
Abstract
Protein-protein interactions are at the heart of regulatory and signaling processes in the cell. In many interactions, one or both proteins are disordered before association. However, this disorder in the unbound state does not prevent many of these proteins folding to a well-defined, ordered structure in the bound state. Here we examine a typical system, where a small disordered protein (PUMA, p53 upregulated modulator of apoptosis) folds to an α-helix when bound to a groove on the surface of a folded protein (MCL-1, induced myeloid leukemia cell differentiation protein). We follow the association of these proteins using rapid-mixing stopped flow, and examine how the kinetic behavior is perturbed by denaturant and carefully chosen mutations. We demonstrate the utility of methods developed for the study of monomeric protein folding, including β-Tanford values, Leffler α, Φ-value analysis, and coarse-grained simulations, and propose a self-consistent mechanism for binding. Folding of the disordered protein before binding does not appear to be required and few, if any, specific interactions are required to commit to association. The majority of PUMA folding occurs after the transition state, in the presence of MCL-1. We also examine the role of the side chains of folded MCL-1 that make up the binding groove and find that many favor equilibrium binding but, surprisingly, inhibit the association 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.