Evidence map›Paper›PMID 34799735›Full record

ArticleNature chemical biology2021

A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes.

Yu-Shiuan Cheng, Tianyi Zhang, Xiang Ma, Sarida Pratuangtham, Grace C Zhang, Alexander A Ondrus, Amirhossein Mafi, Brett Lomenick, Jeffrey J Jones, Alison E Ondrus

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Article
  3. Asymmetric Dynamics Between the Protomers of the σ2 Receptor Homodimer.Journal of chemical information and modeling · 2025
    Article
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  6. Review
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  12. Highly specific σProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  13. Review
  14. Highly specific σbioRxiv : the preprint server for biology · 2023
    Article
  15. Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis.International journal of molecular sciences · 2023
    Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. σScientific reports · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 2 countries.

Yu-Shiuan ChengDepartment of Chemistry, Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-7408-7888
Tianyi ZhangDepartment of Chemistry, Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0001-8289-3102
Xiang MaDepartment of Chemistry, Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-9164-8608
Sarida PratuangthamDepartment of Chemistry, Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
Grace C ZhangDepartment of Chemistry, Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
Alexander A OndrusMathematics Department, Northern Alberta Institute of Technology, Edmonton, Alberta, Canada.ORCID http://orcid.org/0000-0002-3997-6807
Amirhossein MafiDepartment of Chemistry, Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-8366-6785
Brett LomenickProteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-5023-9998
Jeffrey J JonesProteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USA.
Alison E OndrusDepartment of Chemistry, Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA, USA. aondrus@caltech.edu.ORCID http://orcid.org/0000-0002-6023-3290
California Institute of Technology · US

Funding

PREDOCTORAL TRAINING IN BIOLOGY AND CHEMISTRYT32GM007616 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI STERNBERG, PAUL WARREN · 1985 to 2019
$22.9M
Purchase of a nanoLC-QTRAP Mass Spectrometer for Targeted Proteomics StudiesS10OD010788 · OD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI HESS, SONJA · 2013 to 2013
$600k
Acquisition of a Q-Exactive Plus mass spectrometer.S10OD020013 · OD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI HESS, SONJA · 2015 to 2015
$600k
NIGMS NIH HHS T32 GM007616NIH HHS S10 OD010788NIH HHS S10 OD020013
6 · The paper itself

Abstract

Oxysterols (OHCs) are hydroxylated cholesterol metabolites that play ubiquitous roles in health and disease. Due to the non-covalent nature of their interactions and their unique partitioning in membranes, the analysis of live-cell, proteome-wide interactions of OHCs remains an unmet challenge. Here, we present a structurally precise chemoproteomics probe for the biologically active molecule 20(S)-hydroxycholesterol (20(S)-OHC) and provide a map of its proteome-wide targets in the membranes of living cells. Our target catalog consolidates diverse OHC ontologies and demonstrates that OHC-interacting proteins cluster with specific processes in immune response and cancer. Competition experiments reveal that 20(S)-OHC is a chemo-, regio- and stereoselective ligand for the protein transmembrane protein 97 (Tmem97/the σ2 receptor), enabling us to reconstruct the 20(S)-OHC-Tmem97 binding site. Our results demonstrate that multiplexed, quantitative analysis of cellular target engagement can expose new dimensions of metabolite activity and identify actionable targets for molecular therapy.

Indexed as

3T3 CellsAnimalsCell CommunicationCell MembraneClick ChemistryDiazomethaneHEK293 CellsHumansHydroxycholesterolsLigandsMiceProteomePyridinium CompoundsStreptavidinDiazomethaneHydroxycholesterolsLigandsProteomepyridinium chlorochromatePyridinium CompoundsStreptavidin

Identifiers

PMID34799735
PMCPMC8607797
OpenAlexW3133174712

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.