Evidence map›Paper›PMID 27529180›Full record

ArticleBiochemistry2016

Tuning the Binding Affinities and Reversion Kinetics of a Light Inducible Dimer Allows Control of Transmembrane Protein Localization.

Seth P Zimmerman, Ryan A Hallett, Ashley M Bourke, James E Bear, Matthew J Kennedy, Brian Kuhlman

Abstract read
In one paragraph

Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing 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

54 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Optogenetic control of PLC-γ1 activity polarizes cell motility.bioRxiv : the preprint server for biology · 2025
    Article
  7. Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Standardized Parts for Activation of Small GTPase Signaling in Living Cells.Angewandte Chemie (International ed. in English) · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Shining a light on RhoA: Optical control of cell contractility.The international journal of biochemistry & cell biology · 2023
    Review
  18. Article
  19. Optogenetics at the presynapse.Nature neuroscience · 2022
    Review
  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

6 authors.

Seth P Zimmerman
Ryan A Hallett
Ashley M BourkeDepartment of Pharmacology, University of Colorado School of Medicine , Aurora, Colorado 80045, United States.
James E Bear
Matthew J KennedyDepartment of Pharmacology, University of Colorado School of Medicine , Aurora, Colorado 80045, United States.
Brian Kuhlman

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
PREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM007635 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI DELL'ACQUA, MARK L · 1985 to 2023
$6.1M
MOLECULAR AND CELLULAR BIOPHYSICS TRAINING PROGRAMT32GM008570 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KUHLMAN, BRIAN A, SLEP, KEVIN C · 1995 to 2022
$5.1M
Designing Affinity and Specificity at Protein InterfacesR01GM073960 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KUHLMAN, BRIAN A · 2005 to 2018
$3.1M
Spatiotemporal Control of the Epigenome via Photoactivatable Nuclear LocalizationR01DA036877 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAHN, KLAUS M., KUHLMAN, BRIAN A · 2013 to 2017
$2.1M
Mechanisms of dendritic exocytosisR01NS082271 · NINDS · UNIVERSITY OF COLORADO DENVER · PI KENNEDY, MATTHEW J · 2013 to 2017
$1.7M
The role of the Arp2/3 complex in cellular actin dynamicsR01GM111557 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BEAR, JAMES E · 2014 to 2018
$1.5M
Mechanisms of mesenchymal chemotaxisR01GM110155 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BEAR, JAMES E, HAUGH, JASON M. · 2014 to 2017
$1.4M
NCI NIH HHS P30 CA016086NIDA NIH HHS R01 DA036877NIGMS NIH HHS R01 GM073960NIGMS NIH HHS R01 GM110155NIGMS NIH HHS R01 GM111557NIGMS NIH HHS T32 GM007635NIGMS NIH HHS T32 GM008570NINDS NIH HHS R01 NS082271
6 · The paper itself

Abstract

Inducible dimers are powerful tools for controlling biological processes through colocalizing signaling molecules. To be effective, an inducible system should have a dissociation constant in the "off" state that is greater (i.e., weaker affinity) than the concentrations of the molecules that are being controlled, and in the "on" state a dissociation constant that is less (i.e., stronger affinity) than the relevant protein concentrations. Here, we reengineer the interaction between the light inducible dimer, iLID, and its binding partner SspB, to better control proteins present at high effective concentrations (5-100 μM). iLID contains a light-oxygen-voltage (LOV) domain that undergoes a conformational change upon activation with blue light and exposes a peptide motif, ssrA, that binds to SspB. The new variant of the dimer system contains a single SspB point mutation (A58V), and displays a 42-fold change in binding affinity when activated with blue light (from 3 ± 2 μM to 125 ± 40 μM) and allows for light-activated colocalization of transmembrane proteins in neurons, where a higher affinity switch (0.8-47 μM) was less effective because more colocalization was seen in the dark. Additionally, with a point mutation in the LOV domain (N414L), we lengthened the reversion half-life of iLID. This expanded suite of light induced dimers increases the variety of cellular pathways that can be targeted with light.

Indexed as

LightAnimalsCells, CulturedDimerizationKineticsMembrane ProteinsMiceMembrane Proteins

Identifiers

PMID27529180
PMCPMC5332220

What OpenQuestion holds

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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.