ArticleJournal of the American Chemical Society2018
A Thermodynamic Model for Multivalency in 14-3-3 Protein-Protein Interactions.
Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 72 citations in OpenAlex.
- Walking the tightrope: Balancing opposing cooperativities in dynein assembly.The Journal of biological chemistry · 2026Article
- Walking the Tightrope: Balancing Opposing Cooperativities as an Operating Principle in Dynein Assembly.bioRxiv : the preprint server for biology · 2026Article
- Discovery of Dimer-Dependent Aminoacrylamide Molecular Glues for 14-3-3 Protein-Protein Interactions.ACS medicinal chemistry letters · 2026Article
- 14-3-3 binding maintains the Parkinson's associated kinase LRRK2 in an inactive state.Nature communications · 2025Article
- Stoichiometric 14-3-3ζ binding promotes phospho-Tau microtubule dissociation and reduces aggregation and condensation.Communications biology · 2025Article
- Dynamic interactions of dimeric hub proteins underlie their diverse functions and structures: A comparative analysis of 14-3-3 and LC8.The Journal of biological chemistry · 2025Review
- PairK: Pairwise k-mer alignment for quantifying protein motif conservation in disordered regions.Protein science : a publication of the Protein Society · 2025Article
- Rate-Engineered Plasmon-Enhanced Fluorescence for Real-Time Microsecond Dynamics of Single Biomolecules.Nano letters · 2024Article
- PairK: Pairwise k-mer alignment for quantifying protein motif conservation in disordered regions.bioRxiv : the preprint server for biology · 2024Article
- 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization.Chembiochem : a European journal of chemical biology · 2024Review
- Energetic driving force for LHCII clustering in plant membranes.Science advances · 2023Article
- Pseudotyping Improves the Yield of Functional SARS-CoV-2 Virus-like Particles (VLPs) as Tools for Vaccine and Therapeutic Development.International journal of molecular sciences · 2023Article
- Mismatched covalent and noncovalent templating leads to large coiled coil-templated macrocycles.Chemical science · 2023Article
- Straightforward model construction and analysis of multicomponent biomolecular systems in equilibrium.RSC chemical biology · 2023Article
- Understanding the interaction of 14-3-3 proteins with hDMX and hDM2: a structural and biophysical study.The FEBS journal · 2022Article
- Nanoscale organization of two-dimensional multimeric pMHC reagents with DNA origami for CD8Nature communications · 2022Article
- Contemporary biophysical approaches for studying 14-3-3 protein-protein interactions.Frontiers in molecular biosciences · 2022Review
- Improved RAD51 binders through motif shuffling based on the modularity of BRC repeats.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Pathways to Parkinson's disease: a spotlight on 14-3-3 proteins.NPJ Parkinson's disease · 2021Review
- 14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases.Trends in pharmacological sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-protein interactions (PPIs) are at the core of molecular control over cellular function. Multivalency in PPI formation, such as via proteins with multiple binding sites and different valencies, requires fundamental understanding to address correlated challenges in pathologies and drug development. Thermodynamic binding models are needed to provide frameworks for describing multivalent PPIs. We established a model based on ditopic host-guest systems featuring the effective molarity, a hallmark property of multivalency, as a prime parameter governing the intramolecular binding in divalent interactions. By way of illustration, we study the interaction of the bivalent 14-3-3 protein scaffold with both the nonavalent CFTR and the hexavalent LRRK2 proteins, determining the underlying thermodynamics and providing insights into the role of individual sites in the context of the multivalent platform. Fitting of binding data reveals enthalpy-entropy correlation in both systems. Simulations of speciations for the entire phosphorylated protein domains reveal that the CFTR protein preferably binds to 14-3-3 by combinations including the strongest binding site pS768, but that other binding sites take over when this site is eliminated, leading to only a minor decrease in total affinity for 14-3-3. For LRRK2, two binding sites dominate the complex formation with 14-3-3, but the distantly located pS1444 site also plays a role in complex formation. Thermodynamic modeling of these multivalent PPIs allowed analyzing and predicting the effects of individual sites regarding their modulation via, for example, (de)phosphorylation or small-molecule targeting. The results specifically bring forward the potential of PPI stabilization, as an entry for drug discovery for multivalent PPIs.
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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.