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12:27
Measuring Peptide Translocation into Large Unilamellar Vesicles
Published on: January 27, 2012
Transmembrane pores formed by human antimicrobial peptide LL-37
Chang-Chun Lee1, Yen Sun, Shuo Qian
1Department of Physics and Astronomy, Rice University, Houston, Texas, USA.
Biophysical Journal
|April 6, 2011
Summary
Human cathelicidin LL-37 forms transmembrane pores by aligning helices perpendicular to the membrane. This pore formation mechanism, observed in swollen membranes, clarifies LL-37
Area of Science:
- Biophysics
- Biochemistry
- Membrane Biology
Background:
- Human cathelicidin LL-37 exhibits broad-spectrum antimicrobial activity via membrane permeabilization.
- Previous studies suggested a carpet-like mechanism for LL-37 membrane disruption.
- The precise molecular mechanism of LL-37-induced membrane permeabilization remained unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of membrane permeabilization by human cathelicidin LL-37.
- To investigate LL-37's interaction with lipid bilayers and identify pore formation.
- To understand the influence of membrane hydration on LL-37's orientation and function.
Main Methods:
- Utilized oriented circular dichroism, neutron in-plane scattering, and X-ray lamellar diffraction.
- Investigated LL-37 in swollen stacked membranes to achieve normal orientation.
- Compared findings with effects on giant unilamellar vesicles.
Main Results:
- Detected transmembrane pores induced by LL-37 with a water channel radius of 23-33 Å.
- Observed LL-37 helices aligning approximately normal to the membrane during pore formation.
- Found LL-37 adopts a normal orientation only in swollen membranes with spacing exceeding its hydrated value.
Conclusions:
- LL-37 forms transmembrane pores, contradicting previous carpet-like mechanism models.
- The pore formation mechanism aligns with the two-state model seen in other small pore-forming peptides.
- Membrane hydration significantly impacts the orientation and interaction of membrane-active peptides like LL-37.
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