Abstract
Actinoporins constitute a unique class of pore-forming toxins found in sea anemones that are able to bind and oligomerize in membranes, leading to cell swelling, impairment of ionic gradients and, eventually, to cell death. In this review we summarize the knowledge generated from the combination of biochemical and biophysical approaches to the study of sticholysins I and II (Sts, StI/II), two actinoporins largely characterized by the Center of Protein Studies at the University of Havana during the last 20 years. These approaches include strategies for understanding the toxin structure–function relationship, the protein–membrane association process leading to pore formation and the interaction of toxin with cells. The rational combination of experimental and theoretical tools have allowed unraveling, at least partially, of the complex mechanisms involved in toxin–membrane interaction and of the molecular pathways triggered upon this interaction. The study of actinoporins is important not only to gain an understanding of their biological roles in anemone venom but also to investigate basic molecular mechanisms of protein insertion into membranes, protein–lipid interactions and the modulation of protein conformation by lipid binding. A deeper knowledge of the basic molecular mechanisms involved in Sts–cell interaction, as described in this review, will support the current investigations conducted by our group which focus on the design of immunotoxins against tumor cells and antigen-releasing systems to cell cytosol as Sts-based vaccine platforms.
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UR (F/4616-1/2), AV (F/4574-1/2), LP (F/5194-1/2), CS (F4617-1) and SC (5193-1) were recipients of International Foundation for Science Grants (Sweden). This work has been partially supported by a CAPES-MES (Brazil–Cuba) Binational Collaboration Project (111/11).
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Carlos Alvarez declares that he has no conflict of interest. Uris Ros declares that she has no conflict of interest. Aisel Valle declares that he has no conflict of interest. Lohans Pedrera declares that she has no conflict of interest. Carmen Soto declares that she has no conflict of interest. Yadira P. Hervis declares that she has no conflict of interest. Sheila Cabezas declares that she has no conflict of interest. Pedro A. Valiente declares that he has no conflict of interest. Fabiola Pazos declares that she has no conflict of interest. Maria E. Lanio declares that she has no conflict of interest.
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This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri.
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Alvarez, C., Ros, U., Valle, A. et al. Biophysical and biochemical strategies to understand membrane binding and pore formation by sticholysins, pore-forming proteins from a sea anemone. Biophys Rev 9, 529–544 (2017). https://doi.org/10.1007/s12551-017-0316-0
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DOI: https://doi.org/10.1007/s12551-017-0316-0