title: Probing the molecular dynamics of the ABC multidrug transporter LmrA by deuterium solid-state nuclear magnetic resonance.
abstract: The molecular dynamics of the 64 kDa ABC multidrug efflux pump LmrA from Lactococcus lactis within lipid membranes has been investigated by deuterium solid-state NMR. Deuteriomethyl-labeled alanine has been used to probe global protein backbone dynamics. A comparison of static deuterium NMR spectra of full-length LmrA in the resting state and its isolated transmembrane domain revealed a high mobility for the nucleotide binding domains. Their motional freedom is restricted upon ATP binding as seen for LmrA in complex with AMP-PNP, a nonhydrolyzable ATP analogue. LmrA returns to full motional flexibility in the posthydrolysis, vanadate-trapped state. These experiments provide insight into the molecular dynamics of a full-length ABC transporter during the catalytic cycle. Data are discussed in the context of known biochemical data and structural models of ABC transporters.
authors.affiliation: Institute for Biophysical Chemistry and Centre for Biomolecular Magnetic Resonance, J. W. Goethe Universität, Frankfurt am Main, Germany.
authors.forename: Alena
authors.initials: A
authors.lastname: Siarheyeva
authors.forename: Jakob J
authors.initials: JJ
authors.lastname: Lopez
authors.forename: Ines
authors.initials: I
authors.lastname: Lehner
authors.forename: Ute A
authors.initials: UA
authors.lastname: Hellmich
authors.forename: Hendrik W
authors.initials: HW
authors.lastname: van Veen
authors.forename: Clemens
authors.initials: C
authors.lastname: Glaubitz
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D003903:Deuterium; D004591:Electrophoresis, Polyacrylamide Gel; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010759:Phosphorus Isotopes
chemical_list: D000409:Alanine; D001426:Bacterial Proteins; D003903:Deuterium; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010759:Phosphorus Isotopes; C101824:LmrA protein, Lactococcus lactis