title: Lipids modulate the conformational dynamics of a secondary multidrug transporter.
abstract: 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. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers.
authors.affiliation: Department of Chemistry, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Chloé
authors.initials: C
authors.lastname: Martens
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stein
authors.affiliation: Department of Chemistry, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Masureel
authors.affiliation: Department of Chemistry, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Roth
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Smriti
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Department of Chemistry, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Rosie
authors.initials: R
authors.lastname: Dawaliby
authors.affiliation: Department of Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Albert
authors.initials: A
authors.lastname: Konijnenberg
authors.affiliation: Department of Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.affiliation: Department of Chemistry, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Cédric
authors.initials: C
authors.lastname: Govaerts
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Hassane S
authors.initials: HS
authors.lastname: Mchaourab
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002308:Cardiolipins / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013294:Lactococcus lactis; D008563:Membrane Lipids / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: D001426:Bacterial Proteins; D002308:Cardiolipins; C096807:LmrP protein, Lactococcus lactis; D008563:Membrane Lipids; D026901:Membrane Transport Proteins