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Small-Anion Selective Transmembrane "Holes" Induced by an Antimicrobial Peptide Too Short to Span Membranes.
- Source :
-
The journal of physical chemistry. B [J Phys Chem B] 2015 Jul 09; Vol. 119 (27), pp. 8553-60. Date of Electronic Publication: 2015 Jun 30. - Publication Year :
- 2015
-
Abstract
- Whereas many membrane-destabilization modes have been suggested for membrane-spanning antimicrobial peptides (AMPs), few are available for those too short to span membrane thickness. Here we show that ORB-1, a 15-residue disulfide-bridged AMP that is only ∼20 Å long even when fully stretched like a hairpin, may act by inducing small anion-selective transmembrane "holes" of negative mean curvature. In model membranes of Gram-negative bacteria, ORB-1 induces chloride transmembrane transport and formation of transmembrane channels of negative mean curvature, whereas the inactive analogue, ORB-N, does not, suggesting a correlation between antibacterial activity and ability to induce transmembrane channels. Given that ORB-N is the C-terminus amidated form of ORB-1, our results further suggest that formation of membrane-spanning dimers may be required to initiate the observed channel induction. Moreover, ORB-1 renders model bacterial membranes permeable to anions with effective hydration diameters of <1 nm (e.g., Cl(-) and NO3(-)), but not cations of similar sizes (e.g., H3O(+)), indicative of anion-selective transmembrane channels with an effective inner diameter of ≤1 nm. In addition, negative-intrinsic-curvature (NIC) lipids such as phosphoethanolamine (PE) may facilitate the membrane-destabilization process of ORB-1. Our findings may expand current understandings on how AMPs destabilize membranes and facilitate the pharmaceutical development of ORB-1.
- Subjects :
- Anions chemistry
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacology
Antimicrobial Cationic Peptides chemistry
Cell Membrane drug effects
Cell Membrane metabolism
Dimerization
Escherichia coli drug effects
Escherichia coli metabolism
Hemolysis
Ion Channels chemistry
Ion Transport
Models, Biological
Phosphatidylethanolamines chemistry
Phosphatidylglycerols chemistry
Staphylococcus aureus drug effects
Staphylococcus aureus metabolism
Unilamellar Liposomes chemistry
Anions metabolism
Antimicrobial Cationic Peptides metabolism
Ion Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5207
- Volume :
- 119
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- The journal of physical chemistry. B
- Publication Type :
- Academic Journal
- Accession number :
- 26126210
- Full Text :
- https://doi.org/10.1021/acs.jpcb.5b03133