Evidence map›Paper›PMID 34599176›Full record

ArticleNature communications2021

A rational blueprint for the design of chemically-controlled protein switches.

Sailan Shui, Pablo Gainza, Leo Scheller, Che Yang, Yoichi Kurumida, Stéphane Rosset, Sandrine Georgeon, Raphaël B Di Roberto, Rocío Castellanos-Rueda, Sai T Reddy and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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

23 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. AI-GuidedJournal of the American Chemical Society · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. A Designed ZnJournal of the American Chemical Society · 2025
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Turn-On Protein Switches for Controlling Actin Binding in Cells.bioRxiv : the preprint server for biology · 2023
    Article
  15. Article
  16. Rational design of small-molecule responsive protein switches.Protein science : a publication of the Protein Society · 2023
    Review
  17. Article
  18. Engineered PROTAC-CID Systems for Mammalian Inducible Gene Regulation.Journal of the American Chemical Society · 2023
    Article
  19. Article
  20. Article
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

11 authors at 3 institutions in 2 countries.

Sailan ShuiLaboratory of Protein Design and Immunoengineering (LPDI) - STI - EPFL, Lausanne, Switzerland.
Pablo GainzaLaboratory of Protein Design and Immunoengineering (LPDI) - STI - EPFL, Lausanne, Switzerland.ORCID 0000-0001-9197-0982
Leo SchellerLaboratory of Protein Design and Immunoengineering (LPDI) - STI - EPFL, Lausanne, Switzerland.ORCID 0000-0003-2490-4015
Che YangLaboratory of Protein Design and Immunoengineering (LPDI) - STI - EPFL, Lausanne, Switzerland.ORCID 0000-0002-4591-5373
Yoichi KurumidaDepartment of Life Science, School and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Meguro-ku, Tokyo, 152-8550, Japan.
Stéphane RossetLaboratory of Protein Design and Immunoengineering (LPDI) - STI - EPFL, Lausanne, Switzerland.
Sandrine GeorgeonLaboratory of Protein Design and Immunoengineering (LPDI) - STI - EPFL, Lausanne, Switzerland.ORCID 0000-0002-8158-4508
Raphaël B Di RobertoDepartment of Biosystems Science and Engineering, ETH Zürich, 4058, Basel, Switzerland.ORCID 0000-0003-0976-5395
Rocío Castellanos-RuedaDepartment of Biosystems Science and Engineering, ETH Zürich, 4058, Basel, Switzerland.ORCID 0000-0002-9674-4172
Sai T ReddyDepartment of Biosystems Science and Engineering, ETH Zürich, 4058, Basel, Switzerland.
Bruno E CorreiaLaboratory of Protein Design and Immunoengineering (LPDI) - STI - EPFL, Lausanne, Switzerland. bruno.correia@epfl.ch.ORCID 0000-0002-7377-8636
SIB Swiss Institute of Bioinformatics · CHETH Zurich · CHTokyo Institute of Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small-molecule responsive protein switches are crucial components to control synthetic cellular activities. However, the repertoire of small-molecule protein switches is insufficient for many applications, including those in the translational spaces, where properties such as safety, immunogenicity, drug half-life, and drug side-effects are critical. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions as OFF- and ON-switches. The designed binders and drug-receptors form chemically-disruptable heterodimers (CDH) which dissociate in the presence of small molecules. To design ON-switches, we converted the CDHs into a multi-domain architecture which we refer to as activation by inhibitor release switches (AIR) that incorporate a rationally designed drug-insensitive receptor protein. CDHs and AIRs showed excellent performance as drug responsive switches to control combinations of synthetic circuits in mammalian cells. This approach effectively expands the chemical space and logic responses in living cells and provides a blueprint to develop new ON- and OFF-switches.

Indexed as

Computer-Aided DesignHEK293 CellsHumansProtein MultimerizationReceptors, DrugSynthetic BiologyReceptors, Drug

Identifiers

PMID34599176
PMCPMC8486872
OpenAlexW3204297934

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.