Toroidal pores formed by antimicrobial peptides show significant disorder

Sengupta, Durba, Leontidaou, Hari, Mark, Alan E. and Marrink, Siewert-Jan (2008) Toroidal pores formed by antimicrobial peptides show significant disorder. Biochimica et Biophysica Acta: Biomembranes, 2008 1778: 2308-2317. doi:10.1016/j.bbamem.2008.06.007


Author Sengupta, Durba
Leontidaou, Hari
Mark, Alan E.
Marrink, Siewert-Jan
Title Toroidal pores formed by antimicrobial peptides show significant disorder
Journal name Biochimica et Biophysica Acta: Biomembranes   Check publisher's open access policy
ISSN 0005-2736
Publication date 2008-10-01
Sub-type Article (original research)
DOI 10.1016/j.bbamem.2008.06.007
Volume 2008
Issue 1778
Start page 2308
End page 2317
Total pages 10
Place of publication Amsterdam, The Netherlands
Publisher Elsevier
Language eng
Subject C1
060112 Structural Biology (incl. Macromolecular Modelling)
030406 Proteins and Peptides
970106 Expanding Knowledge in the Biological Sciences
Abstract A large variety of antimicrobial peptides have been shown to act, at least in vitro, by poration of the lipid membrane. The nanometre size of these pores, however, complicates their structural characterization by experimental techniques. Here we use molecular dynamics simulations, to study the interaction of a specific class of antimicrobial peptides, melittin, with a dipalmitoylphosphatidylcholine bilayer in atomic detail. We show that transmembrane pores spontaneously form above a critical peptide to lipid ratio. The lipid molecules bend inwards to form a toroidally shaped pore but with only one or two peptides lining the pore. This is in strong contrast to the traditional models of toroidal pores in which the peptides are assumed to adopt a transmembrane orientation. We find that peptide aggregation, either prior or after binding to the membrane surface, is a prerequisite to pore formation. The presence of a stable helical secondary structure of the peptide, however is not. Furthermore, results obtained with modified peptides point to the importance of electrostatic interactions in the poration process. Removing the charges of the basic amino-acid residues of melittin prevents pore formation. It was also found that in the absence of counter ions pores not only form more rapidly but lead to membrane rupture. The rupture process occurs via a novel recursive poration pathway, which we coin the Droste mechanism.
Keyword Antimicrobial peptide
Melittin
Molecular dynamics simulation
Toroidal pore
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Available online 18 June 2008.

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 211 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 228 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 20 Mar 2009, 22:48:53 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences