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Updated: Apr 8, 2026
Measuring Peptide Translocation into Large Unilamellar Vesicles
Published on: January 27, 2012
Small-Anion Selective Transmembrane "Holes" Induced by an Antimicrobial Peptide Too Short to Span Membranes
Kan Hu, Yunjiang Jiang, Yuntao Xie
1‡Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
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.
Insights
Antimicrobial peptides (AMPs) too short to span membranes can form anion-selective channels. ORB-1 induces transmembrane holes, facilitating anion transport and suggesting a new mechanism for AMP membrane destabilization.
Area of Science:
- Biochemistry
- Membrane Biophysics
- Antimicrobial Peptides
Background:
- Antimicrobial peptides (AMPs) are crucial for innate immunity.
- Many AMPs destabilize bacterial membranes to exert their effect.
- Short AMPs pose a challenge to traditional membrane-spanning models.
Purpose of the Study:
- To investigate the membrane interaction mechanism of the short AMP ORB-1.
- To determine if ORB-1 can induce transmembrane channels.
- To explore the role of membrane curvature and lipid composition in ORB-1 activity.
Main Methods:
- Utilized model membranes mimicking Gram-negative bacteria.
- Assessed transmembrane transport of anions and cations.
- Investigated the role of negative intrinsic curvature (NIC) lipids.
- Compared the activity of ORB-1 with its inactive analogue ORB-N.
Main Results:
- ORB-1 induced the formation of transmembrane channels with negative mean curvature.
- Chloride and nitrate transport was observed, but not cation transport.
- Anion-selective channels with an effective inner diameter of ≤1 nm were formed.
- Negative intrinsic curvature (NIC) lipids like phosphoethanolamine (PE) facilitated ORB-1's membrane destabilization.
Conclusions:
- ORB-1 destabilizes membranes by inducing small, anion-selective transmembrane channels.
- Membrane-spanning dimers of ORB-1 may be required for channel induction.
- This mechanism expands the understanding of how short AMPs interact with and permeabilize bacterial membranes.
- Findings support the pharmaceutical development of ORB-1 as a novel antimicrobial agent.
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