Evidence map›Paper›PMID 24729132›Full record

ArticleProtein science : a publication of the Protein Society2014

Increasing the affinity of selective bZIP-binding peptides through surface residue redesign.

Jenifer B Kaplan, Aaron W Reinke, Amy E Keating

Open access · bronzeAbstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 26 citations in OpenAlex.

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  7. Selective antagonism of cJun for cancer therapy.Journal of experimental & clinical cancer research : CR · 2020
    Review
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  15. Protein engineering in the 21st century.Protein science : a publication of the Protein Society · 2015
    Article
  16. Article
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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

3 authors at 2 institutions in 1 country.

Jenifer B KaplanDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139.
Aaron W Reinke
Amy E Keating
Massachusetts Institute of Technology · USUniversity of California San Diego · US

Funding

PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Analysis and Design of Coiled Coil PartneringR01GM067681 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KEATING, AMY E · 2004 to 2012
$2.9M
NIGMS NIH HHS GM067681NIGMS NIH HHS T32 GM007287
6 · The paper itself

Abstract

The coiled-coil dimer is a prevalent protein interaction motif that is important for many cellular processes. The basic leucine-zipper (bZIP) transcription factors are one family of proteins for which coiled-coil mediated dimerization is essential for function, and misregulation of bZIPs can lead to disease states including cancer. This makes coiled coils attractive protein-protein interaction targets to disrupt using engineered molecules. Previous work designing peptides to compete with native coiled-coil interactions focused primarily on designing the core residues of the interface to achieve affinity and specificity. However, folding studies on the model bZIP GCN4 show that coiled-coil surface residues also contribute to binding affinity. Here we extend a prior study in which peptides were designed to bind tightly and specifically to representative members of each of 20 human bZIP families. These "anti-bZIP" peptides were designed with an emphasis on target-binding specificity, with contributions to design-target specificity and affinity engineered considering only the coiled-coil core residues. High-throughput testing using peptide arrays indicated many successes. We have now measured the binding affinities and specificities of anti-bZIPs that bind to FOS, XBP1, ATF6, and CREBZF in solution and tested whether redesigning the surface residues can increase design-target affinity. Incorporating residues that favor helix formation into the designs increased binding affinities in all cases, providing low-nanomolar binders of each target. However, changes in surface electrostatic interactions sometimes changed the binding specificity of the designed peptides.

Indexed as

Basic-Leucine Zipper Transcription FactorsDrug DesignHumansModels, MolecularPeptidesProtein Array AnalysisProtein BindingProtein ConformationProtein Structure, SecondaryStatic ElectricityBasic-Leucine Zipper Transcription FactorsPeptidesbZIP transcription factorscoiled coilhelix propensityprotein designprotein-protein interactions

Identifiers

PMID24729132
PMCPMC4088978
OpenAlexW2152766457

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.