Mapping the Targeted Membrane Pore Formation Mechanism by Solution NMR: The Nisin Z and Lipid II Interaction in SDS Micelles
| Autor: | Hsu, S., Breukink, E.J., de Kruijff, B., Kaptein, R., Bonvin, A.M.J.J., van Nuland, N.A.J., Biochemie van Membranen, NMR-spectroscopie, Sub Chem Biol & Organic Chem begr 1-6-12, Chemical Biology 1, Sub NMR Spectroscopy, NMR Spectroscopy 1, Dep Scheikunde |
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| Rok vydání: | 2002 |
| Předmět: |
Protein Conformation
Stereochemistry Molecular Sequence Data Peptidoglycan Biochemistry Micelle Ion Channels Membrane Lipids chemistry.chemical_compound Molecular recognition Taverne Organic chemistry Amino Acid Sequence Nuclear Magnetic Resonance Biomolecular Micelles Nisin Lanthionine Binding Sites Lipid II Temperature Titrimetry Polyisoprenyl Phosphate Oligosaccharides Sodium Dodecyl Sulfate Nuclear magnetic resonance spectroscopy Lantibiotics Amides Uridine Diphosphate N-Acetylmuramic Acid Anti-Bacterial Agents Solutions Carbohydrate Sequence chemistry Solvents Thermodynamics lipids (amino acids peptides and proteins) Protons Heteronuclear single quantum coherence spectroscopy |
| Zdroj: | Biochemistry, 41, 7670. American Chemical Society : Division of Carbohydrate Chemistry |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Nisin is an example of type-A lantibiotics that contain cyclic lanthionine rings and unusual dehydrated amino acids. Among the numerous pore-forming antimicrobial peptides, type-A lantibiotics form an unique family of post-translationally modified peptides. Via the recognition of cell wall precursor lipid II, nisin has the capacity to form pores against Gram-positive bacteria with an extremely high activity in the nanomolar (nM) range. Here we report a high-resolution NMR spectroscopy study of nisin/lipid II interactions in SDS micelles as a model membrane system in order to elucidate the mechanism of molecular recognition at residue level. The binding to lipid II was studied through (15)N-(1)H HSQC titration, backbone amide proton temperature coefficient analysis, and heteronuclear (15)N[(1)H]-NOE relaxation dynamics experiments. Upon the addition of lipid II, significant changes were monitored in the N-terminal part of nisin. An extremely low amide proton temperature coefficient (Delta delta/Delta T) was found for the amide proton of Ala3 (> -0.1 ppb/K) in the complex form. This suggests tight hydrogen bonding and/or isolation from the bulk solvent for this residue. Large chemical shift perturbations were also observed in the first two rings. In contrast, the C-terminal part of nisin was almost unaffected. This part of the molecule remains flexible and solvent-exposed. On the basis of our results, a multistep pore-forming mechanism is proposed. The N-terminal part of nisin first binds to lipid II, and a subsequent structural rearrangement takes place. The C-terminal part of nisin is possibly responsible for the activation of the pore formation. In light of the emerging antibiotic resistance problems, an understanding of the specific recognition mechanism of nisin with lipid II at the residue specific level may therefore aid in the development of novel antibiotics. |
| Databáze: | OpenAIRE |
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