Evidence map›Paper›PMID 38487241›Full record

ArticleChemical science2024

High-throughput assay exploiting disorder-to-order conformational switches: application to the proteasomal Rpn10:E6AP complex.

Christine S Muli, Sergey G Tarasov, Kylie J Walters

Open access · diamondAbstract read
In one paragraph

Article in Chemical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. 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

3 authors at 1 institution in 1 country.

Christine S MuliProtein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health Frederick MD 21702 USA kylie.walters@nih.gov.ORCID https://orcid.org/0000-0003-1373-3062
Sergey G TarasovBiophysics Resource, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health Frederick MD 21702 USA.ORCID https://orcid.org/0000-0002-7134-0374
Kylie J WaltersProtein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health Frederick MD 21702 USA kylie.walters@nih.gov.ORCID https://orcid.org/0000-0001-7590-2891
National Institutes of Health · US

Funding

Ubiquitin signaling for protein degradationZIABC011490 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WALTERS, KYLIE · 2013 to 2025
$21.1M
CCR Biophysics Resource CoreZICBC010965 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TARASOV, SERGEY · 2009 to 2025
$10.5M
6 · The paper itself

Abstract

Conformational switching is pervasively driven by protein interactions, particularly for intrinsically disordered binding partners. We developed a dually orthogonal fluorescence-based assay to monitor such events, exploiting environmentally sensitive fluorophores. This assay is applied to E3 ligase E6AP, as its AZUL domain induces a disorder-to-order switch in an intrinsically disordered region of the proteasome, the so-named Rpn10 AZUL-binding domain (RAZUL). By testing various fluorophores, we developed an assay appropriate for high-throughput screening of Rpn10:E6AP-disrupting ligands. We found distinct positions in RAZUL for fluorophore labeling with either acrylodan or Atto610, which had disparate spectral responses to E6AP binding. E6AP caused a hypsochromic shift with increased fluorescence of acrylodan-RAZUL while decreasing fluorescence intensity of Atto610-RAZUL. Combining RAZUL labeled with either acrylodan or Atto610 into a common sample achieved robust and orthogonal measurement of the E6AP-induced conformational switch. This approach is generally applicable to disorder-to-order (or

Identifiers

PMID38487241
PMCPMC10935766
OpenAlexW4391564401

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Registered trials

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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.