Evidence map›Paper›PMID 37992806›Full record

ArticleThe Journal of biological chemistry2023

mRNA display reveals a class of high-affinity bromodomain-binding motifs that are not found in the human proteome.

Jason K K Low, Karishma Patel, Natasha Jones, Paul Solomon, Alexander Norman, Joshua W C Maxwell, Petr Pachl, Jacqueline M Matthews, Richard J Payne, Toby Passioura and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

13 authors at 3 institutions in 3 countries.

Jason K K LowSchool of Life and Environmental Sciences, University of Sydney, New South Wales, Australia.
Karishma PatelSchool of Life and Environmental Sciences, University of Sydney, New South Wales, Australia.
Natasha JonesSchool of Life and Environmental Sciences, University of Sydney, New South Wales, Australia.
Paul SolomonSchool of Life and Environmental Sciences, University of Sydney, New South Wales, Australia.
Alexander NormanSchool of Chemistry, University of Sydney, New South Wales, Australia.
Joshua W C MaxwellSchool of Chemistry, University of Sydney, New South Wales, Australia.
Petr PachlSchool of Life and Environmental Sciences, University of Sydney, New South Wales, Australia.
Jacqueline M MatthewsSchool of Life and Environmental Sciences, University of Sydney, New South Wales, Australia.
Richard J PayneSchool of Chemistry, University of Sydney, New South Wales, Australia.
Toby PassiouraSchool of Life and Environmental Sciences, University of Sydney, New South Wales, Australia; Department of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan.
Hiroaki SugaDepartment of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan.
Louise J WalportDepartment of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan; Protein-Protein Interaction Laboratory, The Francis Crick Institute, London, United Kingdom; Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, United Kingdom. Electronic address: louise.walport@crick.ac.uk.
Joel P MackaySchool of Life and Environmental Sciences, University of Sydney, New South Wales, Australia. Electronic address: joel.mackay@sydney.edu.au.
The University of Sydney · AUThe Francis Crick Institute · GBThe University of Tokyo · JP

Funding

Cancer Research UKMedical Research CouncilWellcome Trust CC2030
6 · The paper itself

Abstract

Bromodomains (BDs) regulate gene expression by recognizing protein motifs containing acetyllysine. Although originally characterized as histone-binding proteins, it has since become clear that these domains interact with other acetylated proteins, perhaps most prominently transcription factors. The likely transient nature and low stoichiometry of such modifications, however, has made it challenging to fully define the interactome of any given BD. To begin to address this knowledge gap in an unbiased manner, we carried out mRNA display screens against a BD-the N-terminal BD of BRD3-using peptide libraries that contained either one or two acetyllysine residues. We discovered peptides with very strong consensus sequences and with affinities that are significantly higher than typical BD-peptide interactions. X-ray crystal structures also revealed modes of binding that have not been seen with natural ligands. Intriguingly, however, our sequences are not found in the human proteome, perhaps suggesting that strong binders to BDs might have been selected against during evolution.

Indexed as

ProteomeTranscription FactorsAcetylationAmino Acid MotifsHumansPeptidesProtein BindingProtein DomainsPeptidesProteomeTranscription FactorsBET bromodomainBRD3mRNA displaystructural biology

Identifiers

PMID37992806
PMCPMC10758951
OpenAlexW4388822104

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.