Detail publikace

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

ROY, S. ROY, S. MAHATA, B. PRAMANIK, J. HENNRICH, M. GAVIN, A. TEICHMANN, S.

Originální název

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

Typ

článek v časopise ve Web of Science, Jimp

Jazyk

angličtina

Originální abstrakt

Pregnenolone (P5) is synthesized as the first bioactive steroid in the mitochondria from cholesterol. Clusters of differentiation 4 (CD4+) and Clusters of differentiation 8 (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 T helper cell type 2 (Th2) cells. Subsequently, using high-throughput quantitative proteomics, we identified the P5 interactome in CD4+ Th2 cells. Our study revealed P5’s mode of action in CD4+ immune cells. We identified novel proteins from mitochondrial and endoplasmic reticulum membranes to be the primary mediators of P5’s biochemistry in CD4+ and to concur with our earlier finding in CD8+ immune cells. Applying advanced computational algorithms and molecular simulations, we were able to generate near-native maps of P5–protein key molecular interactions. We showed bonds and interactions between key amino acids and P5, which revealed the importance of ionic bond, hydrophobic interactions, and water channels. We point out that our results can lead to designing of novel molecular therapeutics strategies.

Klíčová slova

pregnenolone, lymphosteroid, chemoproteomics, TH2, click chemistry

Autoři

ROY, S.; ROY, S.; MAHATA, B.; PRAMANIK, J.; HENNRICH, M.; GAVIN, A.; TEICHMANN, S.

Vydáno

31. 10. 2023

Nakladatel

Frontiers

Místo

Švýcarsko

ISSN

1664-3224

Periodikum

Frontiers in Immunology

Ročník

14

Číslo

1

Stát

Švýcarská konfederace

Strany od

1

Strany do

17

Strany počet

17

URL

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229703/full

Plný text v Digitální knihovně

http://hdl.handle.net/11012/245071

BibTex

@article{BUT185331,
  author="Sougata {Roy} and Sudeep {Roy} and Bidesh {Mahata} and Jhuma {Pramanik} and Marco L. {Hennrich} and Anne-Claude {Gavin} and Sarah A. {Teichmann}",
  title="CLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells",
  journal="Frontiers in Immunology",
  year="2023",
  volume="14",
  number="1",
  pages="17",
  doi="10.3389/fimmu.2023.1229703",
  issn="1664-3224",
  url="https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229703/full"
}