4Z9V

TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL

Summary for 4Z9V

• Entry DOI: 10.2210/pdb4z9v/pdb
• Descriptor: Bcl-2-like protein 1,APOPTOSIS REGULATOR BCL-XL, Translationally-controlled tumor protein, BICARBONATE ION, ... (5 entities in total)
• Functional Keywords: tctp, apoptose, bh3, apoptosis
• Biological source: Homo sapiens (Human); More
• Cellular location: Isoform Bcl-X(L): Mitochondrion inner membrane : Q07817; Cytoplasm : P13693
• Total number of polymer chains: 8
• Total formula weight: 49913.77

Authors

Cura, V.,Agez, M.,Thebault, S.,Cavarelli, J. (deposition date: 2015-04-12, release date: 2016-02-10, Last modification date: 2024-11-06)

Primary citation

Thebault, S.,Agez, M.,Chi, X.,Stojko, J.,Cura, V.,Telerman, S.B.,Maillet, L.,Gautier, F.,Billas-Massobrio, I.,Birck, C.,Troffer-Charlier, N.,Karafin, T.,Honore, J.,Senff-Ribeiro, A.,Montessuit, S.,Johnson, C.M.,Juin, P.,Cianferani, S.,Martinou, J.C.,Andrews, D.W.,Amson, R.,Telerman, A.,Cavarelli, J.
TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL.
Sci Rep, 6:19725-19725, 2016

PubMed Abstract: Translationally 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.

PubMed: 26813996
DOI: 10.1038/srep19725

Experimental method

X-RAY DIFFRACTION (2.099 Å)