| First Author | Ohno Y | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 11 | Pages | 108248 |
| PubMed ID | 37965138 | Mgi Jnum | J:342598 |
| Mgi Id | MGI:7550151 | Doi | 10.1016/j.isci.2023.108248 |
| Citation | Ohno Y, et al. (2023) Determining the structure of protein-bound ceramides, essential lipids for skin barrier function. iScience 26(11):108248 |
| abstractText | Protein-bound ceramides, specialized ceramides covalently bound to corneocyte surface proteins, are essential for skin permeability barrier function. However, their exact structure and target amino acid residues are unknown. Here, we found that epoxy-enone (EE) ceramides, precursors of protein-bound ceramides, as well as their synthetic analog, formed stable conjugates only with Cys among nucleophilic amino acids. NMR spectroscopy revealed that the beta-carbon of the enone was attached by the thiol group of Cys via a Michael addition reaction. We confirmed the presence of Cys-bound EE ceramides in mouse epidermis by mass spectrometry analysis of protease-digested epidermis samples. EE ceramides were reversibly released from protein-bound ceramides via sulfoxide elimination. We found that protein-bound ceramides with reversible release properties accounted for approximately 60% of total protein-bound ceramides, indicating that Cys-bound EE ceramides are the predominant protein-bound ceramides. Our findings provide clues to the molecular mechanism of skin barrier formation by protein-bound ceramides. |
