Decoupling immunomodulatory properties from lipid binding in the α-pore-forming toxin Sticholysin II.

Autor: Rivero-Hernández AL; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: ada.rivero-hernandez@biophys.mpg.de., Hervis YP; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; Sorbonne Université, École normale supérieure, PSL University, CNRS, Laboratoire des Biomolécules, LBM, 75005 Paris, France., Valdés-Tresanco ME; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; Center for Molecular Simulations and Department of Biological Sciences, University of Calgary, Alberta T2N 1N4, Canada. Electronic address: mario.valdeztresanco@ucalgary.ca., Escalona-Rodríguez FA; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: felipe@fbio.uh.cu., Cancelliere R; Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, Rome 00133, Italy. Electronic address: rocco.cancelliere@uniroma2.it., Relova-Hernández E; Center of Molecular Immunology, Havana 11600, Cuba. Electronic address: ernestor@cim.sld.cu., Romero-Hernández G; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: glenda.romerohernand@ucalgary.ca., Pérez-Rivera E; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba., Torres-Palacios Y; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: yusniel.torres@fbio.uh.cu., Cartaya-Quintero P; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba., Ros U; Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne 50931, Germany. Electronic address: Uris.Ros@biophys.mpg.de., Porchetta A; Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, Rome 00133, Italy. Electronic address: alessandro.porchetta@uniroma2.it., Micheli L; Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, Rome 00133, Italy. Electronic address: laura.micheli@uniroma2.it., Fernández LE; Center of Molecular Immunology, Havana 11600, Cuba. Electronic address: luis@cim.sld.cu., Laborde R; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: radylq@fbio.uh.cu., Álvarez C; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: calvarez@fbio.uh.cu., Sagan S; Sorbonne Université, École normale supérieure, PSL University, CNRS, Laboratoire des Biomolécules, LBM, 75005 Paris, France. Electronic address: sandrine.sagan@sorbonne-universite.fr., Lanio ME; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: mlanio@fbio.uh.cu., Pazos Santos IF; Center for Protein Studies/Department of Biochemistry, Faculty of Biology, University of Havana, Havana 10400, Cuba; NanoCancer, Center of Molecular Immunology (CIM), Havana 11600, Cuba. Electronic address: fpazos@fbio.uh.cu.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Nov; Vol. 280 (Pt 4), pp. 136244. Date of Electronic Publication: 2024 Oct 03.
DOI: 10.1016/j.ijbiomac.2024.136244
Abstrakt: Sticholysin II (StII), a pore-forming toxin from the marine anemone Stichodactyla helianthus, enhances an antigen-specific cytotoxic T lymphocyte (CTL) response when co-encapsulated in liposomes with a model antigen. This capacity does not depend exclusively on its pore-forming activity and is partially supported by its ability to activate Toll-like receptor 4 (TLR4) in dendritic cells, presumably by interacting with this receptor or by triggering signaling cascades upon binding to lipid membrane. In order to investigate whether the lipid binding capacity of StII is required for immunomodulation, we designed a mutant in which the aromatic amino acids from the interfacial binding site Trp110, Tyr111 and Trp114 were substituted by Ala. In the present work, we demonstrated that StII3A keeps the secondary structure composition and global folding of StII, while it loses its lipid binding and permeabilization abilities. Despite this, StII3A upregulates dendritic cells maturation markers, enhances an antigen-specific effector CD8+ T cells response and confers antitumor protection in a preventive scenario in C57BL/6 mice. Our results indicate that a mechanism independent of its lipid binding ability is involved in the immunomodulatory capacity of StII, pointing to StII3A as a promising candidate to improve the reliability of the Sts-based vaccine platform.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: