Authors:
Stéphanie Thébault, Stéphanie Thébault, Morgane Agez, Morgane Agez, Xiaoke Chi, Xiaoke Chi, Johann Stojko, V. Cura, Stephanie B. Telerman, Stephanie B. Telerman, Laurent Maillet, Fabien Gautier, Isabelle Billas-Massobrio, Catherine Birck, Nathali (...)
Stéphanie Thébault, Stéphanie Thébault, Morgane Agez, Morgane Agez, Xiaoke Chi, Xiaoke Chi, Johann Stojko, V. Cura, Stephanie B. Telerman, Stephanie B. Telerman, Laurent Maillet, Fabien Gautier, Isabelle Billas-Massobrio, Catherine Birck, Nathalie Troffer-Charlier, Teele Karafin, Teele Karafin, Joane Honoré, Andrea Senff-Ribeiro, Andrea Senff-Ribeiro, Sylvie Montessuit, Christopher M. Johnson, Philippe Juin, Sarah Cianférani, Jean-Claude Martinou, David W. Andrews, David W. Andrews, Robert Amson, Robert Amson, Adam Telerman, Adam Telerman, Jean Cavarelli
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Abstract:
AbstractTranslationally Controlled Tumor Protein (TCTP) is anti-apoptotic, key in development and cancer, however without the typical Bcl2 family members’ structure. Here we report that TCTP contains a BH3-like domain and forms heterocomplexes with Bcl-xL. The crystal structure of a Bcl-xL deletion variant-TCTP11–31 complex reveals that TCTP refolds in a helical conformation upon binding the BH3-groove of Bcl-xL, although lacking the h1-subregion interaction. E (...)
AbstractTranslationally Controlled Tumor Protein (TCTP) is anti-apoptotic, key in development and cancer, however without the typical Bcl2 family members’ structure. Here we report that TCTP contains a BH3-like domain and forms heterocomplexes with Bcl-xL. The crystal structure of a Bcl-xL deletion variant-TCTP11–31 complex reveals that TCTP refolds in a helical conformation upon binding the BH3-groove of Bcl-xL, although lacking the h1-subregion interaction. Experiments using in vitro-vivo reconstituted systems and TCTP+/− mice indicate that TCTP activates the anti-apoptotic function of Bcl-xL, in contrast to all other BH3-proteins. Replacing the non-conserved h1 of TCTP by that of Bax drastically increases the affinity of this hybrid for Bcl-xL, modifying its biological properties. This work reveals a novel class of BH3-proteins potentiating the anti-apoptotic function of Bcl-xL.
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