Structural Analysis of Breast-Milk α_S1-Casein: An α-Helical Conformation Is Required for TLR4-Stimulation.

ABSTRACT: Breast-milk α_S1-casein is a Toll-like receptor 4 (TLR4) agonist, whereas phosphorylated α_S1-casein does not bind TLR4. The objective of this study was to analyse the structural requirements for these effects. In silico analysis of α_S1-casein indicated high α-helical content with coiled-coil characteristics. This was confirmed by CD-spectroscopy, showing the α-helical conformation to be stable between pH 2 and 7.4. After in vitro phosphorylation, the α-helical content was significantly reduced, similar to what it was after incubation at 80 °C. This conformation showed no in vitro induction of IL-8 secretion via TLR4. A synthetic peptide corresponding to V⁷⁷-E⁹² of α_S1-casein induced an IL-8 secretion of 0.95 ng/mL via TLR4. O

SUBMITTER: Saenger T 

PROVIDER: S-EPMC10855866 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature