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Sci Rep. 2016 Jan 27;6:19725. doi: 10.1038/srep19725.

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

Author information

1
Département de Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS UMR 7104, INSERM U964, 1 rue Laurent Fries, BP 10142, F-67404 Illkirch, France.
2
CNRS-UMR 8113, LBPA, École Normale Supérieure, 61 avenue du Président Wilson, 94235 Cachan, France.
3
Institut Gustave Roussy, Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805 Villejuif, France.
4
Sunnybrook Research Institute and Departments of Biochemistry and Medical Biophysics, University of Toronto, 2075 Bayview Ave., Toronto, Ontario, M4N 3M5, Canada.
5
Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. W. Hamilton, Ontario, L8N 3Z5, Canada.
6
Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), IPHC-DSA, Université de Strasbourg, CNRS, UMR7178, 25 rue Becquerel, 67087 Strasbourg, France.
7
King's College London Centre for Stem Cells and Regenerative Medicine, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
8
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
9
Center for Cancer Research Nantes-Angers, UMR 892 Inserm - 6299 CNRS/Université de Nantes, IRS-UN, 8 Quai Moncousu - BP 70721, 44007 Nantes Cedex 1.
10
Institut de Cancérologie de l'Ouest, Centre René Gauducheau Bd Jacques Monod, 44805 Saint Herblain-Nantes cedex.
11
Department of Cell Biology, University of Geneva, 30, quai Ansermet, 1211 Geneva 4, Switzerland.

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.

PMID:
26813996
PMCID:
PMC4728560
DOI:
10.1038/srep19725
[Indexed for MEDLINE]
Free PMC Article

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