Antimicrobial protegrin-1 forms ion channels: Molecular dynamic simulation, atomic force microscopy, and electrical conductance studies

Ricardo Capone, Mirela Mustata, Hyunbum Jang, Fernando Teran Arce, Ruth Nussinov, Ratnesh Lal

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Antimicrobial peptides (AMPs) are an emerging class of antibiotics for controlling health effects of antibioticresistant microbial strains. Protegrin-1 (PG-1) is a model antibiotic among β-sheet AMPs. Antibiotic activity of AMPs involves cell membrane damage, yet their membrane interactions, their 3D membrane-associated structures and the mechanism underlying their ability to disrupt cell membrane are poorly understood. Using complementary approaches, including molecular dynamics simulations, atomic force microscopy (AFM) imaging, and planar lipid bilayer reconstitution, we provide computational and experimental evidence that PG-1, a β-hairpin peptide, forms ion channels. Simulations indicate that PG-1 forms channel-like structures with loosely attached subunits when reconstituted in anionic lipid bilayers. AFM images show the presence of channel-like structures when PG-1 is reconstituted in dioleoylphosphatidylserine/palmitoyloleoyl phosphatidylethanolamine bilayers or added to preformed bilayers. Planar lipid bilayer electrical recordings show multiple single channel conductances that are consistent with the heterogeneous oligomeric channel structures seen in AFM images. PG-1 channel formation seems to be lipid-dependent: PG-1 does not easily show ion channel electrical activity in phosphatidylcholine membranes, but readily shows channel activity in membranes rich in phosphatidylethanolamine or phosphatidylserine. The combined results support a model wherein the β-hairpin PG-1 peptide acts as an antibiotic by altering cell ionic homeostasis through ion channel formation in cell membranes.

Original languageEnglish (US)
Pages (from-to)2644-2652
Number of pages9
JournalBiophysical Journal
Volume98
Issue number11
DOIs
StatePublished - Jun 2 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

Fingerprint

Dive into the research topics of 'Antimicrobial protegrin-1 forms ion channels: Molecular dynamic simulation, atomic force microscopy, and electrical conductance studies'. Together they form a unique fingerprint.

Cite this