Fig. 7: A proposed model for MlaC recruitment/binding and accompanying MlaA conformational changes that facilitate retrograde PL transfer by the OmpC-MlaA-(MlaC) complex.

At the OM, apo-MlaC is preferentially recruited to MlaA via electrostatic interactions between MlaC surface charge patch and MlaA C-terminal tail helix. Subsequent docking of MlaC to the base of the MlaA channel induces a conformational change in MlaA, from an MTSES-inaccessible state (State A, “channel-closed”, residue K184 represented by red star) to an MTSES-accessible state (State B, “channel-open”, residue K184 represented by blue star). Along with the localized membrane thinning caused by MlaA, this conformational change may then facilitate the transfer of PLs from the outer leaflet of the OM into the lipid binding cavity of MlaC. Holo-MlaC then leaves the OmpC-MlaA complex to shuttle the PL ligand to the IM, thus resetting MlaA conformation. Vacuum electrostatic surface representations of MlaC bound with lipids (PDB: 5UWA)^23., and in the unliganded form (PDB: 6GKI)²⁵.