ArticleProceedings of the National Academy of Sciences of the United States of America2000
A ligand-reversible dimerization system for controlling protein-protein interactions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed.
- Concentration-dependent cytoplasmic phase separation of TDP-43 drives aggregation and proteinopathy.The FEBS journal · 2026Article
- Artificial repression looping control by regulated autoinhibition of transcription activator-like effector dimer proteins.Nucleic acids research · 2026Article
- Identification of affinity-optimized peptide binders of a viral protease for chemical genetic applications.Bioorganic & medicinal chemistry letters · 2026Article
- Programming tumor evolution with selection gene drives to proactively combat drug resistance.Nature biotechnology · 2025Article
- Article
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi.eLife · 2024Article
- Condensate functionalization with microtubule motors directs their nucleation in space and allows manipulating RNA localization.The EMBO journal · 2023Article
- Rational design of small-molecule responsive protein switches.Protein science : a publication of the Protein Society · 2023Review
- Rational Design of Chemically Controlled Antibodies and Protein Therapeutics.ACS chemical biology · 2023Article
- RNA at the surface of phase-separated condensates impacts their size and number.Biophysical journal · 2022Article
- Article
- Genetically encoded fluorescent tools: Shining a little light on ER-to-Golgi transport.Free radical biology & medicine · 2022Review
- Protein Nanoparticles: Uniting the Power of Proteins with Engineering Design Approaches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- A rational blueprint for the design of chemically-controlled protein switches.Nature communications · 2021Article
- De novo design of a reversible phosphorylation-dependent switch for membrane targeting.Nature communications · 2021Article
- Single-Cell Quantification of the Transition Temperature of Intracellular Elastin-like Polypeptides.ACS biomaterials science & engineering · 2021Article
- Quantitative Flow Cytometry-Based Assays for Measuring Constitutive Secretion.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Synthetic Biology-Empowered Hydrogels for Medical Diagnostics.Advances in biochemical engineering/biotechnology · 2021Article
- Characterization of Gene Repression by Designed Transcription Activator-like Effector Dimer Proteins.Biophysical journal · 2020Article
- Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemically induced dimerization provides a general way to gain control over intracellular processes. Typically, FK506-binding protein (FKBP) domains are fused to a signaling domain of interest, allowing crosslinking to be initiated by addition of a bivalent FKBP ligand. In the course of protein engineering studies on human FKBP, we discovered that a single point mutation in the ligand-binding site (Phe-36 --> Met) converts the normally monomeric protein into a ligand-reversible dimer. Two-hybrid, gel filtration, analytical ultracentrifugation, and x-ray crystallographic studies show that the mutant (F(M)) forms discrete homodimers with micromolar affinity that can be completely dissociated within minutes by addition of monomeric synthetic ligands. These unexpected properties form the basis for a "reverse dimerization" regulatory system involving F(M) fusion proteins, in which association is the ground state and addition of ligand abolishes interactions. We have used this strategy to rapidly and reversibly aggregate fusion proteins in different cellular compartments, and to provide an off switch for transcription. Reiterated F(M) domains should be generally useful as conditional aggregation domains (CADs) to control intracellular events where rapid, reversible dissolution of interactions is required. Our results also suggest that dimerization is a latent property of the FKBP fold: the crystal structure reveals a remarkably complementary interaction between the monomer binding sites, with only subtle changes in side-chain disposition accounting for the dramatic change in quaternary structure.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.