title: Revealing cell-surface intramolecular interactions in the BlaR1 protein of methicillin-resistant Staphylococcus aureus by NMR spectroscopy.
abstract: In methicillin-resistant Staphylococcus aureus, β-lactam antibiotic resistance is mediated by the transmembrane protein BlaR1. The antibiotic sensor domain BlaR(S) and the L2 loop of BlaR1 are on the membrane surface. We used NMR to investigate interactions between BlaR(S) and a water-soluble peptide from L2. This peptide binds BlaR(S) proximal to the antibiotic acylation site as an amphipathic helix. Acylation of BlaR(S) by penicillin G does not disrupt binding. These results suggest a signal transduction mechanism whereby the L2 helix, partially embedded in the membrane, propagates conformational changes caused by BlaR(S) acylation through the membrane via transmembrane segments, leading to antibiotic resistance.
authors.affiliation: The Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Frederick
authors.forename: Brian D
authors.initials: BD
authors.lastname: Wilson
authors.forename: Jooyoung
authors.initials: J
authors.lastname: Cha
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Peng
mesh_terms: D000215:Acylation; D001426:Bacterial Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000378:metabolism; D017433:Protein Structure, Secondary; D015398:Signal Transduction / Q000502:physiology; D013113:Spin Labels; D047090:beta-Lactams / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D013113:Spin Labels; D047090:beta-Lactams; C569108:BlaR1 protein, Staphylococcus aureus; D008666:Metalloendopeptidases