One site on the apoB-100 specifically binds 17-b-estradiol and regulates the overall structure of LDL

The major protein component (apoB-100) of low-density lipoprotein (LDL) is known as a multipotential molecule whose several functional regions can all be affected by key structural modifications driven by specific domains. Based on our previous report on structural and conformational modifications of apoB-100 in the presence of 17-b-estradiol (E2), we characterized the interaction between E2 and the apoB-100, and further explored the induced alterations in terms of the structural arrangement of the whole LDL particle. We report evidence for the existence on apoB-100 of a single specific and saturable binding site for E2, whose occupancy modifies the overall structure of the protein inducing an increase in the a-helix fraction. As a consequence, the structure of LDL particle is deeply perturbed, with a change in the arrangement of both the outer shell and lipid core and an overall volume shrinkage. The evidence of a regulation of apoB-100 structure by a physiological ligand opens new perspectives in the study of the biological addressing of LDL particle and suggests a novel rationale in the search for mechanisms underlying the beneficial role of E2 in decreasing the risk of early lesions in atherosclerosis.