Biophysical and biochemical strategies to understand membrane binding and pore formation by sticholysins, pore-forming p
- PDF / 898,061 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 100 Downloads / 198 Views
REVIEW
Biophysical and biochemical strategies to understand membrane binding and pore formation by sticholysins, pore-forming proteins from a sea anemone Carlos Alvarez 1 & Uris Ros 1,2 & Aisel Valle 1 & Lohans Pedrera 1 & Carmen Soto 1 & Yadira P. Hervis 1 & Sheila Cabezas 1 & Pedro A. Valiente 1 & Fabiola Pazos 1 & Maria E. Lanio 1
Received: 28 June 2017 / Accepted: 8 August 2017 # International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany 2017
Abstract Actinoporins constitute a unique class of poreforming 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
This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri. * Carlos Alvarez [email protected]
1
Center for Protein Studies, Faculty of Biology, University of Havana, Calle 25 No 455, Vedado, Havana, Cuba
2
Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, 72076 Tübingen, Germany
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 Stsbased vaccine platforms. Keywords Sticholysins . Actinoporins . Pore-forming toxins . Protein–membrane interaction . Hemolytic activity
Introducing the toxins Pore-forming toxins (PFT) are one of the most ancient and spectacular weapons used by living beings to attack or selfdefend. Secreted in soluble form, they undergo conformational changes upon different stimuli, allowing them to create a pore in the host membrane. These toxins exhibit a very broad taxonomic distribution from bacteria to mammals (Gonzalez et al. 2008; Bischofberger et al. 2012; Alves et al. 2014), with bacterial PFT the best characterized to date (Peraro and van der Goot 2016).
Data Loading...
