PH-Dependent Interactions of Apolipophorin-III with a Lipid Disk

Abstract

Apolipophorin-III (ApoLp-III) is required for stabilization of molecular shuttles of lipid fuels in insects and is found to contribute to the insect immune reaction. Rearrangement of its five [Formula: see text]-helices enables ApoLp-III to reversibly associate with lipids. We investigate computationally the conformational changes of ApoLp-III and the pH-dependence of the binding free energy of ApoLp-III association with a lipid disk. A dominant binding mode along with several minor, low population, modes of the ApoLp-III binding to a lipid disk was identified. The pH-dependence of the binding energy for ApoLp-III with the lipid disk is predicted to be significant, with the pH-optimum at pH[Formula: see text]. The calculations suggest that there are no direct interactions between the lipid head groups and titratable residues of ApoLp-III. In the physiological pH range from 6.0 to 9.0, the binding free energy of ApoLp-III with the lipid disk decreases significantly with respect to its optimal value at pH 8.0 (at pH[Formula: see text], it is 1.02[Formula: see text]kcal/mol and at pH[Formula: see text] it is 0.23[Formula: see text]kcal/mol less favorable than at the optimal pH[Formula: see text]), indicating that the pH is an important regulator of ApoLp-III lipid disk association.