Differences in activity of actinoporins are related with the hydrophobicity of their N-terminus
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...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
29 June 2015
|
| In: |
Biochimie
Year: 2015, Jahrgang: 116, Pages: 70-78 |
| DOI: | 10.1016/j.biochi.2015.06.024 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.biochi.2015.06.024 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0300908415002035 
|
| Verfasserangaben: | Uris Ros, Wendy Rodríguez-Vera, Lohans Pedrera, Pedro A. Valiente, Sheila Cabezas, María E. Lanio, Ana J. García-Sáez, Carlos Alvarez |
| Zusammenfassung: | 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. |
|---|---|
| Beschreibung: | Gesehen am 02.07.2020 |
| Beschreibung: | Online Resource |
| DOI: | 10.1016/j.biochi.2015.06.024 |