Reference

Palacios-Ortega, J., García-Linares, S., Rivera-de-Torre, E., Gavilanes, J. G., Martínez-del-Pozo, Á., & Slotte, J. P. (2019). Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction. Biophysical Journal, 116(12), 2253-2265.BiophysJ 2019 07 18

Authors

Juan Palacios Ortega, Sara García Linares, Esperanza Rivera de Torre, José G. Gavilanes, Álvaro Martínez-del-Pozo y J. Peter Slotte.

Abstract

Actinoporins are a group of soluble toxic proteins that bind to membranes containing sphingomyelin (SM) and oli- gomerize to form pores. Sticholysin II (StnII) is a member of the actinoporin family produced by Stichodactyla helianthus. Choles- terol (Chol) is known to enhance the activity of StnII. However, the molecular mechanisms behind this activation have remained obscure, although the activation is not Chol specific but rather sterol specific. To further explore how bilayer lipids affect or are affected by StnII, we have used a multiprobe approach (fluorescent analogs of both Chol and SM) in combination with a series of StnII tryptophan (Trp) mutants to study StnII/bilayer interactions. First, we compared StnII bilayer permeabilization in the pres- ence of Chol or oleoyl-ceramide (OCer). The comparison was done because both Chol and OCer have a 1-hydroxyl, which helps to orient the molecule in the bilayer (although OCer has additional polar functional groups). Both Chol and OCer also have increased affinity for SM, which StnII may recognize. However, our results show that only Chol was able to activate StnII-induced bilayer permeabilization; OCer failed to activate it. To further examine possible Chol/StnII interactions, we measured Fo ̈rster resonance energy transfer between Trp in StnII and cholestatrienol, a fluorescent analog of Chol. We could show higher Fo ̈ rster resonance energy transfer efficiency between cholestatrienol and Trps in position 100 and 114 of StnII when compared to three other Trp positions further away from the bilayer binding region of StnII. Taken together, our results suggest that StnII was able to attract Chol to its vicinity, maybe by showing affinity for Chol. SM interactions are known to be important for StnII binding to bi- layers, and Chol is known to facilitate subsequent permeabilization of the bilayers by StnII. Our results help to better understand the role of these important membrane lipids for the bilayer properties of StnII.

Description

Las actinoporinas, entre las que se encuentra la esticolisina II (StnII) son un grupo de toxinas solubles producidas por anémonas marinas que se unen a las membranas lipídicas reconociendo específicamente esfingomielina, ejerciendo su actividad tóxica oligomerizando y formando poros en la bicapa. En este artículo presentamos, por primera vez, evidencias indicando que el colesterol, conocido por aumentar enormemente la eficacia de estas proteínas, puede interaccionar con StnII, estando dicha interacción probablemente mediada por la esfingomielina.

 

Palacios Ortega Imagen grupo

 

REFERENCIA DEL GRUPO INVESTIGADOR

En el grupo en el que se ha llevado a cabo la investigación buscamos la comprensión a nivel molecular del mecanismo de acción de proteínas tóxicas, con el fin de poder utilizarlas como herramientas biotecnológicas. En la elaboración de este artículo, además, hemos contado con la colaboración del grupo del profesor J. Peter Slotte, de la universidad Åbo Akademi de Turku (Finlandia), experto en el estudio del comportamiento de lípidos y membranas lipídicas.

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