The major
protein component (apoB-100) of
low-density lipoprotein (
LDL) is known as a multipotential molecule the several functional regions of which 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-beta-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, the occupancy of which modifies the overall structure of the
protein, inducing an increase in the alpha-helix fraction. As a consequence, the structure of the
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 the
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.