García-Murria, M.J., Duart, G., Grau, B., Diaz-Beneitez, E., Rodríguez, D., Mingarro, I., Martínez-Gil, L., 2020. Viral Bcl2s' transmembrane domain interact with host Bcl2 proteins to control cellular apoptosis. Nature Communications 11, 6056. DOI: 10.1038/s41467-020-19881-9.
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García-Murria, M.J.*, Duart, G.*, Grau, B., Diaz-Beneitez, E., Rodríguez, D., Mingarro, I., Martínez-Gil, L. *Equal contribution.


Viral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis by interacting with host pro- and anti-apoptotic members of the Bcl2 family. Here, we show that the carboxyl-terminal hydrophobic region of herpesviral and poxviral vBcl2s can operate as transmembrane domains (TMDs) and participate in their homo-oligomerization. Additionally, we show that the viral TMDs mediate interactions with cellular pro- and anti-apoptotic Bcl2 TMDs within the membrane. Furthermore, these intra-membrane interactions among viral and cellular proteins are necessary to control cell death upon an apoptotic stimulus. Therefore, their inhibition represents a new potential therapy against viral infections, which are characterized by short- and long-term deregulation of programmed cell death.


El control viral de la apoptosis se produce mediante la expresión de análogos antiapoptóticos de Bcl2 codificados por el virus. Se cree que estas proteínas modulan la muerte celular programada al interactuar con los miembros celulares de la familia Bcl2. Recientemente, hemos identificado que más allá de las interacciones entre las regiones solubles, previamente bien estudiadas, las interacciones proteína-proteína entre los dominios transmembrana Bcl2 celulares y virales son cruciales para el control viral de la apoptosis.. 

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Nuestro laboratorio estudia los principios básicos que gobiernan la biogénesis, la inserción y el plegamiento de las proteínas de membrana. Nuestro interés se centra en las interacciones proteína-proteína que tienen lugar en el entorno de las membranas biológicas, las cuales son cruciales para comprender y modular la actividad de este importante grupo de proteínas. Para realizar nuestras investigaciones utilizamos un variado abanico de técnicas moleculares que aplicamos tanto a la comprensión de los mecanismos de biosíntesis de las proteínas en las membranas como al estudio de relevantes procesos celulares como son la apoptosis o las infecciones virales.


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