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

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dc.contributor.authorRoy, Sougatacs
dc.contributor.authorRoy, Sudeepcs
dc.contributor.authorMahata, Bideshcs
dc.contributor.authorPramanik, Jhumacs
dc.contributor.authorHennrich, Marco L.cs
dc.contributor.authorGavin, Anne-Claudecs
dc.contributor.authorTeichmann, Sarah A.cs
dc.coverage.issue1cs
dc.coverage.volume14cs
dc.date.issued2023-10-31cs
dc.description.abstractPregnenolone (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.en
dc.formattextcs
dc.format.extent1-17cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationFrontiers in Immunology. 2023, vol. 14, issue 1, p. 1-17.en
dc.identifier.doi10.3389/fimmu.2023.1229703cs
dc.identifier.issn1664-3224cs
dc.identifier.orcid0000-0002-7825-0152cs
dc.identifier.other185331cs
dc.identifier.scopus000000278250152cs
dc.identifier.urihttp://hdl.handle.net/11012/245071
dc.language.isoencs
dc.publisherFrontierscs
dc.relation.ispartofFrontiers in Immunologycs
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fimmu.2023.1229703/fullcs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1664-3224/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectpregnenoloneen
dc.subjectlymphosteroiden
dc.subjectchemoproteomicsen
dc.subjectTH2en
dc.subjectclick chemistryen
dc.titleCLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cellsen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-185331en
sync.item.dbtypeVAVen
sync.item.insts2025.02.03 15:39:59en
sync.item.modts2025.01.17 15:12:26en
thesis.grantorVysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií. Ústav biomedicínského inženýrstvícs
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