静的・動的構造評価による生体脂質複合体形成機構の解明

Abstract

Biomembrane is a place for signal transduction, where protein-membrane interactions are controlled by the membrane environment. This environment could be modified by lipid dynamics, such as interbilayer transport and transbilayer movement, which are governed by lipid transfer proteins and translocase enzymes, respectively. Thus, static and dynamic structural evaluations of the membranes are important to understand the links among function, structure, and dynamics of lipid membranes. This review describes our recent studies for 1) the production of lipid nanoparticles with nonlamellar liquid crystalline phases, 2) membrane-protein interaction that relates to the biogenesis of high-density lipoproteins, and 3) the characterization of lipid transfer dynamics by small-angle neutron scattering (SANS). It was demonstrated that different phospholipids have individual effect on membrane-apolipoprotein A-I (apoA-I) interactions that bring about a discoidal lipid-protein complex formation: Phosphatidylethanolamine, possessing the negative spontaneous curvature, increases both the degree of hydration at the membrane interface and the acyl chain order, and enhances the binding of amphipathic helices. A gel phase-forming lipid, sphingomyelin, forms heterogeneous interface of the mixed membranes and facilitates the discoidal particle formation with apoA-I. Phosphatidylserine partly contributes to a reduction in pH at membrane surface, which induces the conformational change of apoA-I and accelerates the discoidal complex formation. It was also demonstrated that SANS is available as a novel method to determine the dynamics of membrane lipids. This technique is perfectly suited to evaluate the activity of proteins relevant to lipid migrations.