Structural and functional basis for lipid synergy on the activity of the antibacterial peptide ABC transporter McjD
| Autor: | Danny Axford, Konstantinos Beis, Séverine Zirah, Hassanul G. Choudhury, Rohanah Hussain, Carol V. Robinson, Shahid Mehmood, Sylvie Rebuffat, Patrick Becker, D. Peter Tieleman, Valentina Corradi |
|---|---|
| Přispěvatelé: | Department of Chemistry, University of Oxford, University of Oxford [Oxford]-Chemistry Research Laboratory, University of Calgary, Department of Life Sciences, Imperial College London, London, United Kingdom, Membrane Protein Laboratory, Diamond Light Source, DIAMOND Light source, STFC Rutherford Appleton Laboratory (RAL), Science and Technology Facilities Council (STFC), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Biotechnology and Biological Sciences Research Council (BBSRC) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Circular dichroism ATP-binding cassette transporter Tandem mass spectrometry 01 natural sciences Biochemistry structure-function Mass Spectrometry chemistry.chemical_compound Bacteriocins structural biology membrane protein Lipid bilayer ComputingMilieux_MISCELLANEOUS 010304 chemical physics Escherichia coli Proteins Phosphatidylglycerols 11 Medical And Health Sciences [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Anti-Bacterial Agents delipidation lipids (amino acids peptides and proteins) ABC transporter 03 Chemical Sciences Biochemistry & Molecular Biology membrane transport Membrane lipids Molecular Dynamics Simulation 03 medical and health sciences Structure-Activity Relationship Protein Domains lipid Membrane Biology non-denaturing mass spectrometry 0103 physical sciences [CHIM.CRIS]Chemical Sciences/Cristallography Escherichia coli circular dichroism (CD) Molecular Biology Phosphatidylglycerol Cell Biology 06 Biological Sciences Membrane transport [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology molecular dynamics 030104 developmental biology Membrane protein chemistry ATP-Binding Cassette Transporters |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2016, 291 (41), pp.21656-21668. ⟨10.1074/jbc.M116.732107⟩ |
| ISSN: | 1083-351X 0021-9258 |
| DOI: | 10.1074/jbc.M116.732107⟩ |
| Popis: | The lipid bilayer is a dynamic environment that consists of a mixture of lipids with different properties that regulate the function of membrane proteins; these lipids are either annular, masking the protein hydrophobic surface, or specific lipids, essential for protein function. In this study, using tandem mass spectrometry, we have identified specific lipids associated with the Escherichia coli ABC transporter McjD, which translocates the antibacterial peptide MccJ25. Using non-denaturing mass spectrometry, we show that McjD in complex with MccJ25 survives the gas phase. Partial delipidation of McjD resulted in reduced ATPase activity and thermostability as shown by circular dichroism, both of which could be restored upon addition of defined E. coli lipids. We have resolved a phosphatidylglycerol lipid associated with McjD at 3.4 A resolution, whereas molecular dynamic simulations carried out in different lipid environments assessed the binding of specific lipids to McjD. Combined, our data show a synergistic effect of zwitterionic and negatively charged lipids on the activity of McjD; the zwitterionic lipids provide structural stability to McjD, whereas the negatively charged lipids are essential for its function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|