Ionic Hydrogen Bonds and Lipid Packing Defects Determine the Binding Orientation and Insertion Depth of RecA on Multicomponent Lipid Bilayers.

We describe a computational and experimental approach for probing the binding properties of the RecA protein at the surface of anionic membranes. Fluorescence measurements indicate that RecA behaves differently when bound to phosphatidylglycerol (PG)- and cardiolipin (CL)-containing liposomes. We use a multistage computational protocol that integrates an implicit membrane/solvent model, the highly mobile mimetic membrane model, and the full atomistic membrane model to study how different anionic lipids perturb RecA binding to the membrane. With anionic lipids studied here, the binding interface involves three key regions: the N-terminal helix, the DNA binding loop L2, and the M-M7 region. The nature of binding involves both electrostatic interactions between cationic protein residues and lipid polar/charged groups and insertion of hydrophobic residues. The L2 loop contributes more to membrane insertion than the N-terminal helix. More subtle aspects of RecA–membrane interaction are influenced by specific p...