Evidence map›Paper›PMID 23569285›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Rational design of a ligand-controlled protein conformational switch.

Onur Dagliyan, David Shirvanyants, Andrei V Karginov, Feng Ding, Lanette Fee, Srinivas N Chandrasekaran, Christina M Freisinger, Gromoslaw A Smolen, Anna Huttenlocher, Klaus M Hahn and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

74 citing papers in PubMed, 128 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Switchbody, an Antigen-Responsive Enzyme Switch Based on Antibody and Its Working Principle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Optogenetically engineered Septin-7 enhances immune cell infiltration of tumor spheroids.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Allosteric regulation of kinase activity in living cells.bioRxiv : the preprint server for biology · 2023
    Article
  17. Rational design of small-molecule responsive protein switches.Protein science : a publication of the Protein Society · 2023
    Review
  18. Dissecting the Determinants of Domain Insertion Tolerance and Allostery in Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  19. Article
  20. Article

14 more citing papers are in PubMed but not listed here.

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.

Onur DagliyanDepartment of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
David Shirvanyants
Andrei V Karginov
Feng Ding
Lanette Fee
Srinivas N Chandrasekaran
Christina M Freisinger
Gromoslaw A Smolen
Anna Huttenlocher
Klaus M Hahn
Nikolay V Dokholyan
Institute of Molecular Biology and Biophysics · RUUniversity of Wisconsin–Madison · USUniversity of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Molecular & Environmental Toxicology Pre-& Postdoctoral Training ProgramT32ES007015 · NIEHS · UNIVERSITY OF WISCONSIN-MADISON · PI CHRISTOPHER A BRADFIELD · 1985 to 2026
$11.5M
Assemby , dynamics and evolution of cell-cell and cell-matrix adhesionsU01GM094663 · NIGMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI GINSBERG, MARK HOWARD · 2010 to 2014
$6.4M
Protein Misfolding and AggregationR01GM080742 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOKHOLYAN, NIKOLAY · 2007 to 2015
$2.8M
A toolkit for imaging and photo-manipulation of signaling in zebrafishR01GM102924 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HAHN, KLAUS M., HUTTENLOCHER, ANNA · 2012 to 2015
$2.5M
Molecular and Cellular Mechanisms of Tumor DevelopmentT32CA157322 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI ALEXANDER, CAROLINE M · 2011 to 2017
$1.6M
New methods for activation of kinases and kinase circuits in living cells.R21CA159179 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V · 2012 to 2013
$371k
Howard Hughes Medical InstituteNCI NIH HHS CA157322NCI NIH HHS P30 CA016086NCI NIH HHS R21 CA159179NCI NIH HHS T32 CA157322NIEHS NIH HHS ES007015NIEHS NIH HHS T32 ES007015NIGMS NIH HHS R01 GM080742NIGMS NIH HHS R01GM080742NIGMS NIH HHS R01 GM102924NIGMS NIH HHS R01GM102924NIGMS NIH HHS U01 GM094663NIGMS NIH HHS U01GM094663
6 · The paper itself

Abstract

Design of a regulatable multistate protein is a challenge for protein engineering. Here we design a protein with a unique topology, called uniRapR, whose conformation is controlled by the binding of a small molecule. We confirm switching and control ability of uniRapR in silico, in vitro, and in vivo. As a proof of concept, uniRapR is used as an artificial regulatory domain to control activity of kinases. By activating Src kinase using uniRapR in single cells and whole organism, we observe two unique phenotypes consistent with its role in metastasis. Activation of Src kinase leads to rapid induction of protrusion with polarized spreading in HeLa cells, and morphological changes with loss of cell-cell contacts in the epidermal tissue of zebrafish. The rational creation of uniRapR exemplifies the strength of computational protein design, and offers a powerful means for targeted activation of many pathways to study signaling in living organisms.

Indexed as

Models, MolecularProtein ConformationAnimalsComputational BiologyEnzyme ActivationEpithelial-Mesenchymal TransitionHeLa CellsHumansLigandsProtein EngineeringProteinssrc-Family KinasesThermodynamicsZebrafishLigandsProteinssrc-Family Kinases

Identifiers

PMID23569285
PMCPMC3637791
OpenAlexW2044476679

What OpenQuestion holds

Textmetadata
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.