4z9v
From Proteopedia
TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL
Structural highlights
Function[B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.[1] [2] Isoform Bcl-X(S) promotes apoptosis.[3] [4] [TCTP_HUMAN] Involved in calcium binding and microtubule stabilization. Publication Abstract from PubMedTranslationally 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. TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL.,Thebault S, Agez M, Chi X, Stojko J, Cura V, Telerman SB, Maillet L, Gautier F, Billas-Massobrio I, Birck C, Troffer-Charlier N, Karafin T, Honore J, Senff-Ribeiro A, Montessuit S, Johnson CM, Juin P, Cianferani S, Martinou JC, Andrews DW, Amson R, Telerman A, Cavarelli J Sci Rep. 2016 Jan 27;6:19725. doi: 10.1038/srep19725. PMID:26813996[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Agez, M | Cavarelli, J | Cura, V | Thebault, S | Apoptose | Apoptosis | Bh3 | Tctp
