Figure 3. Seipin lowers the critical concentration of triacylglycerol (TG) nucleation.
(a) Coarse-grained (CG) model of human seipin oligomer. The CG atoms inside the hydrophobic helix ring represent phospholipid (PL) atoms (proteinized PLs). (b) Elastic network model (ENM) with a spring constant of 0.2 or 2 kcal/mol/Å2. (c) Scaling factors of attraction parameters between seipin–PL and seipin–TG interactions. PL head, interfacial, and tail groups are shown with black, light blue, and dark blue, respectively. TG glycerol and tail groups are shown with green and yellow, respectively. Seipin atoms that attract PL tails are shown with dark blue, and those that attract PL interfacial atoms are shown with sky blue. Two seipin atoms in the hydrophobic helix (HH), shown with yellow, and four central seipin atoms in each transmembrane (TM) segment, shown with dark blue, attract TG atoms. (d) CG molecular dynamics (MD) simulations of bilayers containing 2% TG with a diameter of 40 nm were carried out. The clipped snapshots of the last frames of the pure lipid (left) and seipin-containing systems (center) are shown. The ENM model with a spring constant of 0.2 kcal/mol/Å2 was used. PL head, interfacial, and tail atoms are shown with black, light blue, and dark blue, respectively. TG glycerol and tail atoms are shown with green and yellow, respectively. Seipin oligomer is indicated with red. The nucleation percentages of three systems with simulation steps are shown in right. (e) MARTINI CG model simulations of TG nucleation. TG does not nucleate in the bilayer without seipin (left), while it does in the bilayer with seipin, forming its distinct phase inside the seipin complex (right). Both bilayers have 2% TG, lower than the critical concentration.