Transmembrane Pores Formed by Human Antimicrobial Peptide LL-37

Journal Article · Sat Jan 01 04:00:00 EST 2011 · Biophysical Journal

OSTI ID:1033183

Qian, Shuo ^[1]

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1. ORNL

Human LL-37 is a multifunctional cathelicidin peptide that has shown a wide spectrum of antimicrobial activity by permeabilizing microbial membranes similar to other antimicrobial peptides; however, its molecular mechanism has not been clarified. Two independent experiments revealed LL-37 bound to membranes in the {alpha}-helical form with the axis lying in the plane of membrane. This led to the conclusion that membrane permeabilization by LL-37 is a nonpore carpet-like mechanism of action. Here we report the detection of transmembrane pores induced by LL-37. The pore formation coincided with LL-37 helices aligning approximately normal to the plane of the membrane. We observed an unusual phenomenon of LL-37 embedded in stacked membranes, which are commonly used in peptide orientation studies. The membrane-bound LL-37 was found in the normal orientation only when the membrane spacing in the multilayers exceeded its fully hydrated value. This was achieved by swelling the stacked membranes with excessive water to a swollen state. The transmembrane pores were detected and investigated in swollen states by means of oriented circular dichroism, neutron in-plane scattering, and x-ray lamellar diffraction. The results are consistent with the effect of LL-37 on giant unilamellar vesicles. The detected pores had a water channel of radius 2333 {angstrom}. The molecular mechanism of pore formation by LL-37 is consistent with the two-state model exhibited by magainin and other small pore-forming peptides. The discovery that peptide-membrane interactions in swollen states are different from those in less hydrated states may have implications for other large membrane-active peptides and proteins studied in stacked membranes.

• Research Organization: Oak Ridge National Laboratory (ORNL); High Flux Isotope Reactor; Center for Structural Molecular Biology
• Sponsoring Organization: SC USDOE - Office of Science (SC)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 1033183
• Journal Information: Biophysical Journal, Journal Name: Biophysical Journal Journal Issue: 7 Vol. 100; ISSN 0006-3495; ISSN BIOJAU
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ANTIMICROBIAL AGENTS
DETECTION
DICHROISM
DIFFRACTION
MEMBRANES
NEUTRON DIFFRACTION
ORIENTATION
PEPTIDES
PROTEINS
SCATTERING
SWELLING
WATER
X-RAY DIFFRACTION