Marine sponge cyclic peptide theonellamide A disrupts lipid bilayer integrity without forming distinct membrane pores

Rafael Atillo Espiritu, Kimberly Cornelio, Masanao Kinoshita, Nobuaki Matsumori, Michio Murata, Shinichi Nishimura, Hideaki Kakeya, Minoru Yoshida, Shigeki Matsunaga

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides derived from the marine sponge Theonella sp. These peptides specifically bind to 3β-hydroxysterols, resulting in 1,3-β-d-glucan overproduction and membrane damage in yeasts. The inclusion of cholesterol or ergosterol in phosphatidylcholine membranes significantly enhanced the membrane affinity of theonellamide A (TNM-A) because of its direct interaction with 3β-hydroxyl groups of sterols. To better understand TNM-induced membrane alterations, we investigated the effects of TNM-A on liposome morphology. 31P nuclear magnetic resonance (NMR) and dynamic light scattering (DLS) measurements revealed that the premixing of TNM-A with lipids induced smaller vesicle formation. When giant unilamellar vesicles were incubated with exogenously added TNM-A, confocal micrographs showed dynamic changes in membrane morphology, which were more frequently observed in cholesterol-containing than sterol-free liposomes. In conjunction with our previous data, these results suggest that the membrane action of TNM-A proceeds in two steps: 1) TNM-A binds to the membrane surface through direct interaction with sterols and 2) accumulated TNM-A modifies the local membrane curvature in a concentration-dependent manner, resulting in dramatic membrane morphological changes and membrane disruption.

Original languageEnglish
Pages (from-to)1373-1379
Number of pages7
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1858
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

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Cyclic Peptides
Lipid bilayers
Lipid Bilayers
Porifera
Membranes
Sterols
Liposomes
Theonella
Cholesterol
theonellamide A
Ergosterol
Unilamellar Liposomes
Glucans
Dynamic light scattering
Phosphatidylcholines
Hydroxyl Radical
Yeast
Magnetic Resonance Spectroscopy
Yeasts
Nuclear magnetic resonance

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Marine sponge cyclic peptide theonellamide A disrupts lipid bilayer integrity without forming distinct membrane pores. / Espiritu, Rafael Atillo; Cornelio, Kimberly; Kinoshita, Masanao; Matsumori, Nobuaki; Murata, Michio; Nishimura, Shinichi; Kakeya, Hideaki; Yoshida, Minoru; Matsunaga, Shigeki.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1858, No. 6, 01.06.2016, p. 1373-1379.

Research output: Contribution to journalArticle

Espiritu, Rafael Atillo ; Cornelio, Kimberly ; Kinoshita, Masanao ; Matsumori, Nobuaki ; Murata, Michio ; Nishimura, Shinichi ; Kakeya, Hideaki ; Yoshida, Minoru ; Matsunaga, Shigeki. / Marine sponge cyclic peptide theonellamide A disrupts lipid bilayer integrity without forming distinct membrane pores. In: Biochimica et Biophysica Acta - Biomembranes. 2016 ; Vol. 1858, No. 6. pp. 1373-1379.
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