title: Effect of the structural difference between Bax-α5 and Bcl-xL-α5 on their interactions with lipid bilayers.
abstract: Bax-α5 and Bcl-xL-α5, which are shorter versions of apoptosis-regulating proteins Bax and Bcl-xL, were simulated with lipid bilayers composed of pure dioleoylglycerophosphocholine (DOPC) lipids or a mixture of DOPCs and cholesterols. Starting with the initial peptide position near the bilayer surface, both Bax-α5 and Bcl-xL-α5 bind to the bilayer because of their charge interactions with lipid head groups. After binding to the bilayer surface, Bax-α5 inserts into the pure DOPC bilayer, but not into the DOPC-cholesterol bilayer, showing the effect of cholesterols on the peptide-bilayer interaction. Despite the similar peptide structure, Bcl-xL-α5 does not insert into the bilayer, in contrast to the interaction of Bax-α5 with the bilayer. Bcl-xL-α5 predominantly has the random-coil structure in both aqueous and membrane environments, while Bax-α5 shows a higher extent of α-helical structure in the bilayer than in water, in quantitative agreement with experiment. In particular, although Bax-α5 and Bcl-xL-α5 have the same extent of the electrostatic interaction with lipid head groups, Bax-α5 has stronger hydrophobic interaction with lipid tails than does Bcl-xL-α5. These indicate that Bax-α5 retains α-helical structure, where hydrophobic residues on one side of the α-helix interact with lipid tails and thus can easily attract the peptide into the lipid-tail region, while Bcl-xL-α5 forms a random coil that tends to spread on the bilayer surface and thus has weaker hydrophobic interaction with lipid tails. Our findings help explain the experimental observation that showed that Bax-α5 disorders lipids and induces pore formation, but Bcl-xL-α5 does not.
authors.affiliation: Department of Chemical Engineering, Dankook University, Yongin, 448-701, South Korea. leeh@dankook.ac.kr.
authors.forename: Eol
authors.initials: E
authors.lastname: Han
authors.forename: Hwankyu
authors.initials: H
authors.lastname: Lee
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D055672:Static Electricity; D051028:bcl-2-Associated X Protein / Q000737:chemistry*; D051020:bcl-X Protein / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein