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Clavanin permeabilizes target membranes via two distinctly different pH-dependent mechanisms
Ellen J M van Kan1, Rudy A Demel, Eefjan Breukink
1Department Coating Systems and Active Ingredients, Renewable Resources, Agrotechnological Research Institute, Wageningen University and Research Centre, Bornsesteeg 59, 6708 PD Wageningen, The Netherlands. e.j.m.vankan@ato.wag-ur.nl
Biochemistry
|June 12, 2002
Summary
Clavanin A, a peptide antibiotic, exhibits distinct pH-dependent membrane activities. At low pH, it targets membrane proteins to disrupt ion gradients, unlike its neutral pH mechanism.
Area of Science:
- Antimicrobial peptide research
- Membrane biophysics
- Biochemistry
Background:
- Clavanin A is a peptide antibiotic rich in histidine and glycine residues.
- Understanding its pH-dependent activity is crucial for its therapeutic potential.
Purpose of the Study:
- To investigate the pH-dependent antimicrobial and membrane interaction mechanisms of clavanin A.
- To elucidate the distinct modes of action at neutral versus acidic pH.
Main Methods:
- Growth inhibition assays with Lactobacillus sake.
- Membrane leakage experiments using unilamellar vesicles.
- Analysis of transmembrane proton and ion gradients.
Main Results:
- Clavanin A showed enhanced antimicrobial activity against Lactobacillus sake at lower pH.
- At neutral pH, clavanin A non-specifically permeabilized membranes, but not at low pH.
- At low pH, clavanin A disrupted proton and ion gradients, suggesting membrane protein targets.
Conclusions:
- Clavanin A possesses two distinct pH-dependent modes of action.
- At low pH, clavanin A targets membrane proteins, facilitated by its histidine and glycine residues.
- The peptide's unique conformational flexibility contributes to its dual membrane activity.