| First Author | Cheng YS | Year | 2021 |
| Journal | Nat Chem Biol | Volume | 17 |
| Issue | 12 | Pages | 1271-1280 |
| PubMed ID | 34799735 | Mgi Jnum | J:343398 |
| Mgi Id | MGI:7565905 | Doi | 10.1038/s41589-021-00907-2 |
| Citation | Cheng YS, et al. (2021) A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes. Nat Chem Biol 17(12):1271-1280 |
| abstractText | 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 sigma2 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. |
