Evidence map›Paper›PMID 38228615›Full record

ArticleCell discovery2024

Designed allosteric protein logic.

Tjaša Plaper, Estera Merljak, Tina Fink, Tadej Satler, Ajasja Ljubetič, Duško Lainšček, Vid Jazbec, Mojca Benčina, Sintija Stevanoska, Sašo Džeroski and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Tjaša Plaper *Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.ORCID http://orcid.org/0000-0001-9452-7193
Estera Merljak *Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.ORCID http://orcid.org/0000-0003-2830-1166
Tina Fink *Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
Tadej SatlerDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
Ajasja LjubetičDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
Duško LainščekDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
Vid JazbecDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.ORCID http://orcid.org/0000-0003-2326-153X
Mojca BenčinaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
Sintija StevanoskaDepartment of knowledge technologies, Jožef Stefan Institute, Jamova cesta 39, 1000, Ljubljana, Slovenia.
Sašo DžeroskiDepartment of knowledge technologies, Jožef Stefan Institute, Jamova cesta 39, 1000, Ljubljana, Slovenia.
Roman JeralaDepartment of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia. roman.jerala@ki.si.ORCID http://orcid.org/0000-0002-6337-5251
National Institute of Chemistry · SIJožef Stefan Institute · SIUniversity of Ljubljana · SI

Funding

Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency) J1-4406Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency) J1-9173Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency) N4-0080Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency) N7-0800Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency) P4-0167Javna Agencija za Raziskovalno Dejavnost RS (Slovenian Research Agency) Z4-2657
6 · The paper itself

Abstract

The regulation of protein function by external or internal signals is one of the key features of living organisms. The ability to directly control the function of a selected protein would represent a valuable tool for regulating biological processes. Here, we present a generally applicable regulation of proteins called INSRTR, based on inserting a peptide into a loop of a target protein that retains its function. We demonstrate the versatility and robustness of coiled-coil-mediated regulation, which enables designs for either inactivation or activation of selected protein functions, and implementation of two-input logic functions with rapid response in mammalian cells. The selection of insertion positions in tested proteins was facilitated by using a predictive machine learning model. We showcase the robustness of the INSRTR strategy on proteins with diverse folds and biological functions, including enzymes, signaling mediators, DNA binders, transcriptional regulators, reporters, and antibody domains implemented as chimeric antigen receptors in T cells. Our findings highlight the potential of INSRTR as a powerful tool for precise control of protein function, advancing our understanding of biological processes and developing biotechnological and therapeutic interventions.

Identifiers

PMID38228615
PMCPMC10791696
OpenAlexW4390908261

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.