Evidence map›Paper›PMID 32747768›Full record

ArticleNature methods2020

Rational design and implementation of a chemically inducible heterotrimerization system.

Helen D Wu, Masaki Kikuchi, Onur Dagliyan, Adam K Aragaki, Hideki Nakamura, Nikolay V Dokholyan, Takashi Umehara, Takanari Inoue

Abstract read
In one paragraph

Article in Nature methods, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Sensing and Reprogramming Surface Receptor Activation With Synthetic Transcriptional Circuits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  10. Selective optogenetic inhibition of GαProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Review
  12. Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  13. Article
  14. GAS41 promotes H2A.Z deposition through recognition of the N terminus of histone H3 by the YEATS domain.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Article
  16. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Helen D WuDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-1649-9099
Masaki KikuchiLaboratory for Epigenetics Drug Discovery, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan.
Onur DagliyanDepartment of Neurobiology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1825-1011
Adam K AragakiDepartment of Cell Biology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-9458-0426
Hideki NakamuraDepartment of Cell Biology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nikolay V DokholyanDepartments of Pharmacology and Biochemistry & Molecular Biology, Penn State University College of Medicine, Hershey, PA, USA.ORCID http://orcid.org/0000-0002-8225-4025
Takashi UmeharaLaboratory for Epigenetics Drug Discovery, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan. takashi.umehara@riken.jp.ORCID http://orcid.org/0000-0003-3464-2960
Takanari InoueDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jctinoue@jhmi.edu.ORCID http://orcid.org/0000-0002-7957-7624

Funding

Nanoscale programming of cellular and physiological phenotypes: EquipmentR35GM134864 · NIGMS · UNIVERSITY OF VIRGINIA · PI Nikolay Dokholyan · 2020 to 2026
$5.2M
Engineering allostery for in vivo protein controlR01GM123247 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOKHOLYAN, NIKOLAY · 2017 to 2019
$1.5M
Feedback and Crosstalk in Eukaryotic ChemotaxisR01GM123130 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI INOUE, TAKANARI · 2018 to 2021
$1.5M
NIGMS NIH HHS R01 GM123130NIGMS NIH HHS R01 GM123247NIGMS NIH HHS R35 GM134864
6 · The paper itself

Abstract

Chemically inducible dimerization (CID) uses a small molecule to induce binding of two different proteins. CID tools such as the FK506-binding protein-FKBP-rapamycin-binding- (FKBP-FRB)-rapamycin system have been widely used to probe molecular events inside and outside cells. While various CID tools are available, chemically inducible trimerization (CIT) does not exist, due to inherent challenges in designing a chemical that simultaneously binds three proteins with high affinity and specificity. Here, we developed CIT by rationally splitting FRB and FKBP. Cellular and structural datasets showed efficient trimerization of split pairs of FRB or FKBP with full-length FKBP or FRB, respectively, by rapamycin. CIT rapidly induced tri-organellar junctions and perturbed intended membrane lipids exclusively at select membrane contact sites. By conferring one additional condition to what is achievable with CID, CIT expands the types of manipulation in single live cells to address cell biology questions otherwise intractable and engineer cell functions for future synthetic biology applications.

Indexed as

HeLa CellsHumansModels, MolecularMutationProtein ConformationSirolimusTacrolimus Binding ProteinsTOR Serine-Threonine KinasesMTOR protein, humanSirolimusTacrolimus Binding ProteinsTOR Serine-Threonine Kinases

Identifiers

PMID32747768
PMCPMC9936427

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.