ArticleJournal of the American Chemical Society2017
The Molecular Tweezer CLR01 Stabilizes a Disordered Protein-Protein Interface.
Article in Journal of the American Chemical Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 63 citations in OpenAlex.
- A Rigid Supramolecular Solution to a Flexible Problem: A Multifunctional Calix[4]arene-Based Strategy to Prevent α‑Synuclein Toxicity.ACS central science · 2026Article
- Protein Recognition and Assembly by a Phosphocavitand.Journal of the American Chemical Society · 2025Article
- N-Terminal Protein Binding and Disorder-to-Order Transition by a Synthetic Receptor.Biochemistry · 2025Article
- How Do Molecular Tweezers Bind to Proteins? Lessons from X-ray Crystallography.Molecules (Basel, Switzerland) · 2024Review
- From Tethered to Freestanding Stabilizers of 14-3-3 Protein-Protein Interactions through Fragment Linking.Angewandte Chemie (International ed. in English) · 2023Article
- Biophysical and Integrative Characterization of Protein Intrinsic Disorder as a Prime Target for Drug Discovery.Biomolecules · 2023Review
- Protein-protein interfaces in molecular glue-induced ternary complexes: classification, characterization, and prediction.RSC chemical biology · 2023Review
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- From sequence to function through structure: Deep learning for protein design.Computational and structural biotechnology journal · 2023Review
- Switchable Control of Scaffold Protein Activity via Engineered Phosphoregulated Autoinhibition.ACS synthetic biology · 2022Article
- Exploring the Binding Mechanism of a Supramolecular Tweezer CLR01 to 14-3-3σ ProteinFrontiers in chemistry · 2022Article
- Targeting the Surface of the Protein 14-3-3 by Ultrasmall (1.5 nm) Gold Nanoparticles Carrying the Specific Peptide CRaf.Chembiochem : a European journal of chemical biology · 2021Article
- Specific inhibition of the Survivin-CRM1 interaction by peptide-modified molecular tweezers.Nature communications · 2021Article
- Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson's Disease.Frontiers in immunology · 2021Review
- A new soaking procedure for X-ray crystallographic structural determination of protein-peptide complexes.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Theoretical study of switching characteristics of molecular tweezers based on bis(Zn-salphen).Journal of molecular modeling · 2020Article
- Atomic Details of Carbon-Based Nanomolecules Interacting with Proteins.Molecules (Basel, Switzerland) · 2020Review
- Fragment-based Differential Targeting of PPI Stabilizer Interfaces.Journal of medicinal chemistry · 2020Article
- A Supramolecular Stabilizer of the 14-3-3ζ/ERα Protein-Protein Interaction with a Synergistic Mode of Action.Angewandte Chemie (International ed. in English) · 2020Article
- Dynamic conformational flexibility and molecular interactions of intrinsically disordered proteins.Journal of biosciences · 2020Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein regions that are involved in protein-protein interactions (PPIs) very often display a high degree of intrinsic disorder, which is reduced during the recognition process. A prime example is binding of the rigid 14-3-3 adapter proteins to their numerous partner proteins, whose recognition motifs undergo an extensive disorder-to-order transition. In this context, it is highly desirable to control this entropy-costly process using tailored stabilizing agents. This study reveals how the molecular tweezer CLR01 tunes the 14-3-3/Cdc25CpS216 protein-protein interaction. Protein crystallography, biophysical affinity determination and biomolecular simulations unanimously deliver a remarkable finding: a supramolecular "Janus" ligand can bind simultaneously to a flexible peptidic PPI recognition motif and to a well-structured adapter protein. This binding fills a gap in the protein-protein interface, "freezes" one of the conformational states of the intrinsically disordered Cdc25C protein partner and enhances the apparent affinity of the interaction. This is the first structural and functional proof of a supramolecular ligand targeting a PPI interface and stabilizing the binding of an intrinsically disordered recognition motif to a rigid partner protein.
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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.