Computational Elucidation of Sterol Recognition by SREBP Cleavage Activatory Protein.

ABSTRACT: Intracellular cholesterol homeostasis is regulated by the sterol response element-binding protein (SREBP) pathway through the SREBP cleavage-activating protein (SCAP) and the insulin-induced gene protein (INSIG). Previous studies highlighted that high concentrations of cholesterol mediated the dimerization between INSIG and SCAP, which led to an inhibition of cholesterol uptake and biogenesis. However, the molecular understanding of the SCAP-INSIG and cholesterol interactions remains elusive. Here, we used coarse-grained (CG) and atomistic (AT) molecular dynamics (MD) simulation to determine interactions between INSIG, SCAP, and cholesterol. Our work highlighted the novel binding pocket in the luminal domain at atomistic resolution. Using a combination of the AlphaFold3 model and Go̅-marti

SUBMITTER: Khiewdee C 

PROVIDER: S-EPMC12308794 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature