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PreprintCited by 5Click Chemistry and ApplicationsProtein Interaction Studies and Fluorescence AnalysisAdvanced Proteomics Techniques and Applications

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CLICK- chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells

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Roy, Sougata, Roy, Sudeep, Mahata, Bidesh, Pramanik, Jhuma, Hennrich, Marco L., Gavin, Anne-Claude, Teichmann, Sarah A.·2023·Frontiers in Immunology
DOI 10.1101/2023.05.23.541892PMC PMC10644475

Preprint — published as 10.3389/fimmu.2023.1229703 · Paper page

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Abstract

Pregnenolone (P5) is synthesized as the first bioactive steroid in the mitochondria from cholesterol. CD4+ and CD8+ immune cells synthesize P5 de novo , P5 in turn play important role in immune homeostasis and regulation. However, P5’s biochemical mode of action in immune cells is still emerging. We envisage that revealing the complete spectrum of P5-target proteins in immune cells would have multifold applications, not only in basic understanding of steroids biochemistry in immune cells but also in developing new therapeutic applications. We employed a CLICK-enabled probe to capture P5-binding proteins in live Th2 cells. Subsequently, using high-throughput quantitative proteomics we identified the P5-interactome in CD4+ Th2 cells. Our study revealed P5’s conserved mode of action in CD4+ and CD8+ immune cells. We identified novel proteins from mitochondrial and endoplasmic reticulum membranes to be the primary mediators of P5’s biochemistry in CD4+ and CD8+ immune cells. Applying advanced computational algorithms, we were able to generate near-native maps of P5-protein key molecular interactions that can lead to successful designing of novel molecular therapeutics strategies.

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Metadata

Authors
Roy, S., Roy, S., Mahata, B., Pramanik, J., Hennrich, M. L., Gavin, A.-C., & Teichmann, S. A.
Affiliations
  • Ashoka University (IN)
  • University of Cambridge (GB)
  • European Molecular Biology Laboratory (DE)
  • University of Geneva (CH)
Corresponding author
Roy, Sougata
ORCID
Venue
Frontiers in Immunology
Publisher
openRxiv
Published
2023-05-24
Volume
14
Pages
1229703-1229703
ISSN
1664-3224 (ISSN-L)
DOI
10.1101/2023.05.23.541892
PMC
PMC10644475
OpenAlex
W4388047184
Cited by
5
References
1
Citations by year
2026: 1 · 2025: 2 · 2024: 2
FWCI
0.51
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Brno University of Technology Digital Library (Brno University of Technology) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • National Science Foundation
  • UK Research and Innovation
  • Cancer Research UK (RCCFEL\100095))
  • Louis-Jeantet Foundation
  • Medical Research Council (MR/V028995/1)
  • Biotechnology and Biological Sciences Research Council (BB/V006126/1)
  • European Research Council
  • H2020 European Research Council (646794)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
pregnenolone, steroid binding proteins, Th2 cells, CD4+ T cells, mitochondrial proteins, endoplasmic reticulum proteins
MeSH terms
Carrier Proteins, Pregnenolone, Steroids, Th2 Cells, Molecular Dynamics Simulation

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