2.A.1.3.34
The P55 (MFS55) triglyceride (TAG)/drug efflux pump (Rv141Oc) (extrudes drugs including rifampicin and clifazimine, first- and second-line anti-tuberculosis drugs.) CCCP and valinomycin inhibited drug resistance (Ramón-García et al., 2009).  P55 also exports malachite green, ethidium bromide, isoniazid and ethambutol (Bianco et al. 2011).  It functions together with the outer membrane lipoprotein porin, LprG (P9WK45; TC# 9.B.138.1.1), also called P27 and Lpp-27 (Bianco et al. 2011; Farrow and Rubin 2008).  MFS55 is required together with LprG for normal colony morphology and sliding motility, possibly due to alterred cell wall composition (Farrow and Rubin 2008). MFS transporter Rv1410 and the periplasmic lipoprotein, LprG, transport triacylglycerides (TAGs) that seal the mycomembrane. Remm et al. 2023 reported a 2.7 Å structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ~20 Å into the periplasm. A small, very hydrophobic cavity suitable for lipid transport is constricted by a functionally important ion-lock likely involved in proton coupling. Combining mutational analyses and MD simulations, the authors proposed that TAGs are extracted from the core of the inner membrane into the central cavity via lateral clefts present in the inward-facing conformation. The functional role of the periplasmic helix extensions is to channel the extracted TAG into the lipid binding pocket of LprG (Farrow and Rubin 2008).  MFS55 is required together with LprG for normal colony morphology and sliding motility, possibly due to alterred cell wall composition (Farrow and Rubin 2008). MFS transporter Rv1410 and the periplasmic lipoprotein, LprG, transport triacylglycerides (TAGs) that seal the mycomembrane. Remm et al. 2023 reported a 2.7 Å structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ~20 Å into the periplasm. A small, very hydrophobic cavity suitable for lipid transport is constricted by a functionally important ion-lock likely involved in proton coupling. Combining mutational analyses and MD simulations, the authors proposed that TAGs are extracted from the core of the inner membrane into the central cavity via lateral clefts present in the inward-facing conformation. The functional role of the periplasmic helix extensions is to channel the extracted TAG into the lipid binding pocket of LprG (Remm et al. 2023).