Evidence map›Paper›PMID 25306102›Full record

ReviewTrends in genetics : TIG2014

Engineering allostery.

Srivatsan Raman, Noah Taylor, Naomi Genuth, Stanley Fields, George M Church

Abstract readReview
In one paragraph

Review in Trends in genetics : TIG, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Analysis of the Association of Two SNPs in the Promoter Regions of theAnimals : an open access journal from MDPI · 2022
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Predictive shifts in free energy couple mutations to their phenotypic consequences.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  15. Article
  16. Review
  17. Article
  18. Review
  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

5 authors.

Srivatsan RamanWyss Institute for Biologically-Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: sraman@genetics.med.harvard.edu.
Noah TaylorWyss Institute for Biologically-Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Naomi GenuthWyss Institute for Biologically-Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Stanley FieldsHoward Hughes Medical Institute, Departments of Genome Sciences and Medicine, University of Washington, Seattle, WA 98195, USA.
George M ChurchWyss Institute for Biologically-Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Funding

ZDS2P REGULATES SWE1P-DEPENDENT POLARIZED CELL GROWTH IN S CEREVISIAEP41RR011823 · NCRR · UNIVERSITY OF WASHINGTON · PI FIELDS, STANLEY · 1996 to 2011
$24.7M
TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI YATES III, JOHN R · 2012 to 2021
$20.7M
Howard Hughes Medical InstituteNCRR NIH HHS P41 RR011823NIGMS NIH HHS P41 GM103533
6 · The paper itself

Abstract

Allosteric proteins have great potential in synthetic biology, but our limited understanding of the molecular underpinnings of allostery has hindered the development of designer molecules, including transcription factors with new DNA-binding or ligand-binding specificities that respond appropriately to inducers. Such allosteric proteins could function as novel switches in complex circuits, metabolite sensors, or as orthogonal regulators for independent, inducible control of multiple genes. Advances in DNA synthesis and next-generation sequencing technologies have enabled the assessment of millions of mutants in a single experiment, providing new opportunities to study allostery. Using the classic LacI protein as an example, we describe a genetic selection system using a bidirectional reporter to capture mutants in both allosteric states, allowing the positions most crucial for allostery to be identified. This approach is not limited to bacterial transcription factors, and could reveal new mechanistic insights and facilitate engineering of other major classes of allosteric proteins such as nuclear receptors, two-component systems, G protein-coupled receptors, and protein kinases.

Indexed as

Nucleic Acid ConformationProtein Structure, TertiaryAllosteric RegulationBacterial ProteinsBinding SitesDNA, BacterialModels, MolecularMutationProtein BindingTranscription FactorsBacterial ProteinsDNA, BacterialTranscription Factors

Identifiers

PMID25306102
PMCPMC4254034

What OpenQuestion holds

Textmetadata
LicenceTDM
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.