title: A lipid-dependent link between activity and oligomerization state of the M. tuberculosis SMR protein TBsmr.
abstract: TBsmr is a secondary active multidrug transporter from Mycobacterium tuberculosis that transports a plethora of compounds including antibiotics and fluorescent dyes. It belongs to the small multidrug resistance (SMR) superfamily and is structurally and functionally related to E. coli EmrE. Of particular importance is the link between protein function, oligomeric state and lipid composition. By freeze fracture EM, we found three different size distributions in three different lipid environments for TBsmr indicating different oligomeric states. The link of these states with protein activity has been probed by fluorescence spectroscopy revealing significant differences. The drug binding site has been probed further by (19)F-MAS NMR through chemical labeling of native cysteine residues showing a water accessible environment in agreement with the alternating access model.
authors.affiliation: Institute for Biophysical Chemistry, J.W. Goethe University, Frankfurt, Germany; Centre for Biomolecular Magnetic Resonance, J.W. Goethe University, Frankfurt, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mörs
authors.forename: Ute A
authors.initials: UA
authors.lastname: Hellmich
authors.forename: Daniel
authors.initials: D
authors.lastname: Basting
authors.forename: Philipp
authors.initials: P
authors.lastname: Marchand
authors.forename: Jan Philip
authors.initials: JP
authors.lastname: Wurm
authors.forename: Winfried
authors.initials: W
authors.lastname: Haase
authors.forename: Clemens
authors.initials: C
authors.lastname: Glaubitz
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D017920:Antiporters / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry*; D005614:Freeze Fracturing; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008854:Microscopy, Electron / Q000379:methods; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000737:chemistry*; D013050:Spectrometry, Fluorescence / Q000379:methods; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D017920:Antiporters; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D005456:Fluorescent Dyes; D008055:Lipids; D027701:Organic Cation Transport Proteins; D014867:Water; C075436:EmrE protein, E coli; D003545:Cysteine