Dissecting the mechanism of action of actinoporins. Role of the N-terminal amphipathic α-helix in membrane binding and pore activity of sticholysins I and II

PloS One
Gustavo P B CarreteroShirley Schreier

Abstract

Actinoporins sticholysin I and sticholysin II (St I, St II) are proposed to lyse model and biomembranes via toroidal pore formation by their N-terminal domain. Based on the hypothesis that peptide fragments can reproduce the structure and function of this domain, the behavior of peptides containing St I residues 12-31 (StI12-31), St II residues 11-30 (StII11-30), and its TOAC-labeled analogue (N-TOAC-StII11-30) was examined. Molecular modeling showed a good match with experimental structures, indicating amphipathic α-helices in the same regions as in the toxins. CD spectra revealed that the peptides were essentially unstructured in aqueous solution, acquiring α-helical conformation upon interaction with micelles and large unilamellar vesicles (LUV) of variable lipid composition. Fluorescence quenching studies with NBD-containing lipids indicated that N-TOAC-StII11-30's nitroxide moiety is located in the membranes polar head group region. Pyrene-labeled phospholipid inter-leaflet redistribution suggested that the peptides form toroidal pores, according to the mechanism of action proposed for the toxins. Binding occurred only to negatively charged LUV, indicating the importance of electrostatic interactions; in contrast the pepti...Continue Reading

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Citations

Jan 4, 2019·Protein and Peptide Letters·Esteban N LorenzonEduardo M Cilli
Feb 7, 2020·Natural Product Reports·Anthony R CarrollMichèle R Prinsep
Dec 2, 2020·International Journal of Molecular Sciences·Esperanza Rivera-de-TorreSara García-Linares
Feb 23, 2021·Biophysical Journal·Aliasghar SepehriThemis Lazaridis
Mar 30, 2020·Biochimica Et Biophysica Acta. Biomembranes·José C BozelliRichard M Epand
May 1, 2021·Biomolecules·Gustavo Penteado Battesini CarreteroIolanda Midea Cuccovia
Aug 10, 2021·Frontiers in Molecular Biosciences·Pratima Verma, Kausik Chattopadhyay
May 1, 2020·Biochimica Et Biophysica Acta. Biomembranes·Juan Palacios-OrtegaÁlvaro Martínez-Del-Pozo

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Methods Mentioned

BETA
X-ray
gel-filtration
NMR
Fluorescence
hydrogen

Software Mentioned

UCSF Chimera
GROMACS
FlexStation
FOLD
PEPFIT
Visual Dynamics
PEP
PyMol Educational

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