LmrP from Lactoccoccus lactis: a tractable model to understand secondary multidrug transport in MFS.

The secondary transporter LmrP from Lactoccoccus lactis is a remarkable model to study the molecular basis of secondary multidrug transport. This review article addresses more than twenty years of research about transport activity, substrates range, conformational dynamics and mechanistic models of drug export for LmrP. Several studies have shown that the transporter alternates between inward-open and outward-open conformations and that the transition is regulated by the protonation state of key acidic residues and is further modulated by the lipid environment.

Lipids modulate the conformational dynamics of a secondary multidrug transporter.

Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter.