Roles of integral protein in membrane permeabilization by amphidinols

Nagy Morsy, Keiichi Konoki, Toshihiro Houdai, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Saburo Aimoto

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Amphidinols (AMs) are a group of dinoflagellate metabolites with potent antifungal activity. As is the case with polyene macrolide antibiotics, the mode of action of AMs is accounted for by direct interaction with lipid bilayers, which leads to formation of pores or lesions in biomembranes. However, it was revealed that AMs induce hemolysis with significantly lower concentrations than those necessary to permeabilize artificial liposomes, suggesting that a certain factor(s) in erythrocyte membrane potentiates AM activity. Glycophorin A (GpA), a major erythrocyte protein, was chosen as a model protein to investigate interaction between peptides and AMs such as AM2, AM3 and AM6 by using SDS-PAGE, surface plasmon resonance, and fluorescent-dye leakages from GpA-reconstituted liposomes. The results unambiguously demonstrated that AMs have an affinity to the transmembrane domain of GpA, and their membrane-permeabilizing activity is significantly potentiated by GpA. Surface plasmon resonance experiments revealed that their interaction has a dissociation constant of the order of 10 μM, which is significantly larger than efficacious concentrations of hemolysis by AMs. These results imply that the potentiation action by GpA or membrane integral peptides may be due to a higher affinity of AMs to protein-containing membranes than that to pure lipid bilayers.

Original languageEnglish
Pages (from-to)1453-1459
Number of pages7
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1778
Issue number6
DOIs
Publication statusPublished - Jun 1 2008

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Glycophorin
Membrane Proteins
Membranes
Lipid bilayers
Surface Plasmon Resonance
Lipid Bilayers
Surface plasmon resonance
Hemolysis
Proteins
Liposomes
Polyenes
Dinoflagellida
Peptides
Macrolides
Erythrocyte Membrane
Metabolites
Fluorescent Dyes
Polyacrylamide Gel Electrophoresis
Erythrocytes
Anti-Bacterial Agents

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Roles of integral protein in membrane permeabilization by amphidinols. / Morsy, Nagy; Konoki, Keiichi; Houdai, Toshihiro; Matsumori, Nobuaki; Oishi, Tohru; Murata, Michio; Aimoto, Saburo.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1778, No. 6, 01.06.2008, p. 1453-1459.

Research output: Contribution to journalArticle

Morsy, Nagy ; Konoki, Keiichi ; Houdai, Toshihiro ; Matsumori, Nobuaki ; Oishi, Tohru ; Murata, Michio ; Aimoto, Saburo. / Roles of integral protein in membrane permeabilization by amphidinols. In: Biochimica et Biophysica Acta - Biomembranes. 2008 ; Vol. 1778, No. 6. pp. 1453-1459.
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