Academic Journal
Interactions between phosphatidylethanolamine headgroup and LmrP, a multidrug transporter: a conserved mechanism for proton gradient sensing?
| العنوان: | Interactions between phosphatidylethanolamine headgroup and LmrP, a multidrug transporter: a conserved mechanism for proton gradient sensing? |
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| المؤلفون: | Hakizimana, Pierre, Masureel, Matthieu, Gbaguidi, Bénédicte, Ruysschaert, Jean Marie, Govaerts, Cédric |
| المصدر: | The Journal of biological chemistry, 283 (14 |
| سنة النشر: | 2008 |
| المجموعة: | DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
| مصطلحات موضوعية: | Sciences bio-médicales et agricoles, Biochimie, Biologie, Biologie cellulaire, Biologie moléculaire, Biophysique, Sciences biomédicales, Sciences de la matière vivante, Amino Acid Motifs -- physiology, Amino Acid Substitution, Bacterial Proteins -- chemistry, Bacterial Proteins -- genetics, Bacterial Proteins -- metabolism, Biological Transport -- physiology, Hydrogen Bonding, Lactococcus lactis -- chemistry, Lactococcus lactis -- genetics, Lactococcus lactis -- metabolism, Lipid Bilayers -- chemistry, Lipid Bilayers -- metabolism, Membrane Transport Proteins -- chemistry, Membrane Transport Proteins -- genetics, Membrane Transport Proteins -- metabolism, Phosphatidylcholines -- chemistry, Phosphatidylcholines -- metabolism, Point Mutation, Proton-Motive Force -- physiology, Structure-Activity Relationship |
| الوصف: | In a number of cases, the function of membrane proteins appears to require the presence of specific lipid species in the bilayer. We have shown that the secondary multidrug transporter LmrP requires the presence of phosphatidylethanolamine (PE), as its replacement by phosphatidylcholine (PC) inhibits transport activity and directly affects its structure, although the underlying mechanism was unknown. Here, we show that the effect of PE on the structure and the function of LmrP is mediated by interactions between the lipid headgroup and the protein. We used methyl-PE and dimethyl-PE analogs of PE to show that only replacement of the three hydrogens by methyl moieties leads to changes in the biochemical and biophysical properties of the reconstituted protein. This suggests that LmrP does not depend on the bulk properties of the phospholipids tested but solely on the hydrogen bonding ability of the headgroup. We then show 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. We conclude that the negatively charged Asp-68 is likely to participate in the interaction with PE and that such interaction is required for proton gradient sensing, substrate binding, and transport. Because Asp-68 belongs to a highly conserved motif in the Major Facilitator Superfamily (which includes LacY and EmrD), this interaction might be a general feature of these transporters that is involved in proton gradient sensing and lipid dependence. ; Journal Article ; Research Support, Non-U.S. Gov't ; info:eu-repo/semantics/published |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 2 full-text file(s): application/pdf | application/pdf |
| اللغة: | English |
| Relation: | uri/info:doi/10.1074/jbc.M708427200; uri/info:pii/M708427200; uri/info:pmid/18234676; uri/info:scp/44049083041; https://dipot.ulb.ac.be/dspace/bitstream/2013/59101/4/doi_35305.pdf; https://dipot.ulb.ac.be/dspace/bitstream/2013/59101/1/Hakizimana_et_al_2008_J_Biol_Chem_in_press.pdf; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/59101 |
| الاتاحة: | http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/59101 https://dipot.ulb.ac.be/dspace/bitstream/2013/59101/4/doi_35305.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/59101/1/Hakizimana_et_al_2008_J_Biol_Chem_in_press.pdf |
| رقم الانضمام: | edsbas.18F608D |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |