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@ARTICLE{Ros:127406,
author = {U. Ros and W. Rodríguez-Vera and L. Pedrera and P. A.
Valiente and S. Cabezas and M. E. Lanio and A. J.
García-Sáez$^*$ and C. Alvarez},
title = {{D}ifferences in activity of actinoporins are related with
the hydrophobicity of their {N}-terminus.},
journal = {Biochimie},
volume = {116},
issn = {0300-9084},
address = {Paris [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2017-03429},
pages = {70 - 78},
year = {2015},
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.},
keywords = {Peptides (NLM Chemicals)},
cin = {B160},
ddc = {540},
cid = {I:(DE-He78)B160-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26134716},
doi = {10.1016/j.biochi.2015.06.024},
url = {https://inrepo02.dkfz.de/record/127406},
}