Affordable Access

deepdyve-link
Publisher Website

Experimental and Computational Characterization of Oxidized and Reduced Protegrin Pores in Lipid Bilayers.

Authors
  • Rodnin, Mykola V1
  • Vasquez-Montes, Victor1
  • Nepal, Binod2
  • Ladokhin, Alexey S3
  • Lazaridis, Themis4, 5
  • 1 Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS, 66160, USA.
  • 2 Department of Chemistry and Biochemistry, City College of New York, New York, NY, 10031, USA.
  • 3 Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS, 66160, USA. [email protected]
  • 4 Department of Chemistry and Biochemistry, City College of New York, New York, NY, 10031, USA. [email protected]
  • 5 Graduate Programs in Chemistry, Biochemistry, and Physics, The Graduate Center, City University of New York, New York, NY, 10016, USA. [email protected]
Type
Published Article
Journal
The Journal of Membrane Biology
Publisher
Springer-Verlag
Publication Date
Jun 01, 2020
Volume
253
Issue
3
Pages
287–298
Identifiers
DOI: 10.1007/s00232-020-00124-3
PMID: 32500172
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Protegrin-1 (PG-1), an 18-residue β-hairpin stabilized by two disulfide bonds, is a member of a family of powerful antimicrobial peptides which are believed to act through membrane permeabilization. Here we used a combination of experimental and computational approaches to characterize possible structural arrangements of PG-1 in lipid bilayers mimicking bacterial membranes. We have measured the dose-response function of the PG-1-induced leakage of markers of various sizes from vesicles and found it to be consistent with the formation of pores of two different sizes. The first one allows the release of small dyes and occurs at peptide:lipid ratios < 0.006. Above this ratio, larger pores are observed through which the smallest of dextrans FD4 can be released. In parallel with pore formation, we observe a general large-scale destabilization of vesicles which is probably related to complete rupture of some vesicles. The population of vesicles that are completely ruptured depends linearly on PG-1:lipid ratio. Neither pore size, nor vesicle rupture are influenced by the formation of disulfide bonds. Previous computational work on oxidized protegrin is complemented here by all-atom MD simulations of PG-1 with reduced disulfide bonds both in solution (monomer) and in a bilayer (dimer and octamer). The simulations provide molecular insights into the influence of disulfide bonds on peptide conformation, aggregation, and oligomeric structure.

Report this publication

Statistics

Seen <100 times