Conformational changes in a bacterial multidrug transporter are phosphatidylethanolamine-dependent

@article{Gbaguidi2007ConformationalCI,
  title={Conformational changes in a bacterial multidrug transporter are phosphatidylethanolamine-dependent},
  author={B{\'e}n{\'e}dicte Gbaguidi and Pierre Hakizimana and Guy Vandenbussche and Jean Marie Ruysschaert},
  journal={Cellular and Molecular Life Sciences},
  year={2007},
  volume={64},
  pages={1571-1582}
}
Abstract.LmrP is an electrogenic H+/drug antiporter that extrudes a broad spectrum of antibiotics. Five carboxylic residues are implicated in drug binding (Asp142 and Glu327) and proton motive force-mediated restructuring (Asp68, Asp128 and Asp235). ATR-FTIR (Attenuated Total Reflection — Fourier Transform Infrared) and tryptophan quenching experiments revealed that phosphatidylethanolamine (PE) is required to generate the structural intermediates induced by ionization of carboxylic residues… 
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Interactions between Phosphatidylethanolamine Headgroup and LmrP, a Multidrug Transporter
TLDR
It is shown that a single point mutation in LmrP, D68C, is sufficient to recapitulate precisely every biochemical and biophysical effect observed when PE is replaced by PC, including energy transfer between the protein tryptophan residues and the lipid headgroups.
Protonation drives the conformational switch in the multidrug transporter LmrP.
TLDR
The conformational equilibrium of LmrP, a multidrug transporter from Lactococcus lactis, is uncovered and it is found that the transporter switches between outward-open and outward-closed conformations, depending on the protonation states of specific acidic residues forming a transmembrane protonations relay.
Biochemical and biophysical studies of the prokaryotic proton dependent oligopeptide transporters
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Bacterial POTs are established as model systems for studying the mammalian oligopeptide transporters, and a mechanistic model for peptide transport is proposed.
Hoechst 33342 Is a Hidden “Janus” amongst Substrates for the Multidrug Efflux Pump LmrP
TLDR
Surprisingly, and in contrast to other multidrug transporters, LmrP was found to actively accumulate, rather than extrude, Hoechst 33342 in lactococcal cells, and a hidden “Janus” amongst LMRP substrates is discovered that is translocated in reverse direction across the membrane.
Crystal structure of a prokaryotic homologue of the mammalian oligopeptide–proton symporters, PepT1 and PepT2
TLDR
The crystal structure of PepTSo is presented, a functionally similar prokaryotic homologue of the mammalian peptide transporters from Shewanella oneidensis, which reveals a ligand‐bound occluded state for the MFS and provides new insights into a general transport mechanism.
Lactose permease lipid selectivity using Förster resonance energy transfer.
Molecular organization of nalidixate conjugated calixarenes in bacterial model membranes probed by molecular dynamics simulation and Langmuir monolayer studies.
TLDR
Although both calixarene derivatives increase the chain tilt and conformational disordering of the DMPE molecules, these effects are more important in the case of the monosubstituted derivative.
Plasticity of lipid-protein interactions in the function and topogenesis of the membrane protein lactose permease from Escherichia coli
TLDR
Lactose permease of Escherichia coli exhibits uphill transport and native conformation of P7 when expressed in a mutant of E. coli in which PC completely replaces PE even though the structure is not completely native.
Structure of the YajR transporter suggests a transport mechanism based on the conserved motif A
TLDR
The crystal structure of Escherichia coli YajR is reported, unique in illustrating the functional role of “sequence motif A” and suggests a general mechanism for the conformational change between the inward and outward states of the MFS transporters.
Phosphatidylethanolamine Deficiency Impairs Escherichia coli Adhesion by Downregulating Lipopolysaccharide Synthesis, Which is Reversible by High Galactose/Lactose Cultivation
TLDR
It is found that PE deficiency could impair E. coli adhesion on macrophages or glass coverslips by downregulating lipopolysaccharide (LPS) biosynthesis, which could be reversible by high galactose/lactose but not glucose cultivation, suggesting that targeting PE biosynthesis is also a potential antibacterial strategy.
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References

SHOWING 1-10 OF 45 REFERENCES
Acidic Residues in the Lactococcal Multidrug Efflux Pump LmrP Play Critical Roles in Transport of Lipophilic Cationic Compounds*
TLDR
Surprisingly, the residues Cys142 and Cys327 become accessible for fluorescein maleimide upon binding of substrates, indicating a movement of these residues from a nonpolar to a polar environment.
Secondary and Tertiary Structure Changes of Reconstituted LmrA Induced by Nucleotide Binding or Hydrolysis
TLDR
2H/H exchange and fluorescence quenching studies indicate that the protein undergoes two distinct tertiary structure changes during the hydrolysis process, which means that LmrA alone is poorly accessible to the aqueous medium but adopts a more accessible conformation when ATP Hydrolysis takes place.
Intermediate Structural States Involved in MRP1-mediated Drug Transport
TLDR
Human multidrug resistance protein 1 (MRP1) is a member of the ATP-binding cassette transporter family and transports chemotherapeutic drugs as well as diverse organic anions such as leukotriene LTC4, suggesting that GSH-mediated conformational changes are required for the coupling between drug transport and ATP hydrolysis.
A critical role of a carboxylate in proton conduction by the ATP‐binding cassette multidrug transporter LmrA
TLDR
Functional analyses of wild‐type and mutant proteins in cells and proteoliposomes support the proposal for the mechanistic role of E314 in proton‐coupled ethidium transport.
Proton motive force mediates a reorientation of the cytosolic domains of the multidrug transporter LmrP
TLDR
This study shows that both the proton motive force and ligand interaction alter the accessibility of cytosolic tryptophan residues to a hydrophilic quencher in LmrP, and this drug binding-mediated reorganization may be related to the transition between the high- and low-affinity drug-binding sites.
Membrane Topography of the Coupling Ion Binding Site in Na+-translocating F1F0 ATP Synthase*
TLDR
Na+ in/22Na+ outexchange activity of the ATP synthase was not affected by modifying the c-Glu65 sites with the carbodiimide, but upon photoinduced cross-linking, this activity was abolished.
Monoclonal antibody 4B1 alters the pKa of a carboxylic acid at position 325 (helix X) of the lactose permease of Escherichia coli.
TLDR
P pH profiles for active transport, efflux, and equilibrium exchange are analyzed for wild-type permease and mutant Glu325-->Asp and are consistent with the idea that translocation of the ternary complex between the permease, lactose, and H+ does not tolerate a negative charge at position 325.
Facilitated Drug Influx by an Energy-uncoupled Secondary Multidrug Transporter*
TLDR
A new strategy for eliminating drug-resistant microbial pathogens is suggested, the design and use of modulators of secondary multidrug resistance transporters that uncouple drug efflux from proton influx, thereby allowing transmembrane electrical potential-driven influx of cationic drugs.
Structural and Functional Asymmetry of the Nucleotide-binding Domains of P-glycoprotein Investigated by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy*
TLDR
The dynamic changes occurring during the catalytic cycle of MDR3 P-glycoprotein (Pgp) and the role of each nucleotide-binding domain (NBD) in the transport process were investigated using attenuated total reflection Fourier transform infrared spectroscopy to conclude that the NBDs have an asymmetric structure and different functions.
Unraveling the mechanism of the lactose permease of Escherichia coli.
TLDR
The results offer a mechanistic model for lactose/H(+) symport and show the effect of pH on ligand binding in wild-type lactose permease or mutants in the four residues-Glu-269, Arg-302, His-322, and Glu-325-that are the key participants in H(+) translocation and coupling between sugar and H(+ translocation.
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