Differences in activity of actinoporins are related with the hydrophobicity of their N-terminus

• Verfasst von: Ros, Uris [VerfasserIn]
• Verfasst von: Rodríguez-Vera, Wendy [VerfasserIn]
• Verfasst von: Pedrera, Lohans [VerfasserIn]
• Verfasst von: Valiente, Pedro A. [VerfasserIn]
• Verfasst von: Cabezas, Sheila [VerfasserIn]
• Verfasst von: Lanio, María E. [VerfasserIn]
• Verfasst von: García-Sáez, Ana J. [VerfasserIn]
• Verfasst von: Alvarez, Carlos [VerfasserIn]
• Titel: Differences in activity of actinoporins are related with the hydrophobicity of their N-terminus
• Verf.angabe: Uris Ros, Wendy Rodríguez-Vera, Lohans Pedrera, Pedro A. Valiente, Sheila Cabezas, María E. Lanio, Ana J. García-Sáez, Carlos Alvarez
• E-Jahr: 2015
• Jahr: 29 June 2015
• Umfang: 9 S.
• Fussnoten: Gesehen am 02.07.2020
• Titel Quelle: Enthalten in: Biochimie
• Ort Quelle: Paris [u.a.] : Elsevier, 1971
• Jahr Quelle: 2015
• Band/Heft Quelle: 116(2015), Seite 70-78
• DOI: doi:10.1016/j.biochi.2015.06.024
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Actinoporin
• Sach-SW: Hemolytic activity
• Sach-SW: Peptide-membrane interaction
• Sach-SW: Permeabilizing activity
• Sach-SW: Pore-forming toxins
• K10plus-PPN: 1703324056

Abstract

Actinoporins are pore-forming toxins (PFT) produced by sea anemones with molecular mass around 20 kDa and high affinity for sphingomyelin. The most studied atinoporins are sticholysins I and II (StI/StII) from Stichodactyla helianthus, equinatoxin II (EqtII) from Actinia equina, and fragaceatoxin C (FraC) from Actinia fragacea. Their N-terminal sequences encompassing residues 1-30 seem to be the best candidates for pore formation. This segment comprises an amphipathic α-helix preceded by a more or less hydrophobic segment, depending on the toxin, of around 10 amino acid residues. Although it is clear that the N-terminal is the most variable sequence in this protein family, the role of their hydrophobic segment in not fully understood. Here we show a comparison of StI, StII, EqtII, and FraC activities with that of their respective N-terminal synthetic peptides. The hemolytic and permeabilizing activity of the peptides reproduce qualitatively the behavior of their respective parental proteins and are particularly related to the hydrophobicity of the corresponding 1-10 segment. Furthermore, the dendrogram analysis of actinoporins' N-terminal sequence allows relating differences in alignment with differences in activity among the four toxins. We have also evaluated the penetration depth of the N-terminal segment of StI and StII by using Trp-containing peptide-analogs. Our data suggest that the N-terminus of StII is more deeply buried into the hydrophobic core of the bilayer than that of StI. We hypothesize that the highest activity of StII could be ascribed to a larger hydrophobic continuum, an uninterrupted sequence of non-charged mainly hydrophobic amino acid residues, of its N-terminus promoting a highest ability to partially insert in the membrane core. Moreover, as we show for four related peptides that a higher hydrophobicity contributes to increase the activity, we reinforce the notion that this property must be taken into account to design new potent membranotropic agents.