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PDBsum entry 4z9v
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Contents |
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153 a.a.
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15 a.a.
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16 a.a.
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21 a.a.
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20 a.a.
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PDB id:
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Apoptosis
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Title:
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Tctp contains a bh3-like domain, which instead of inhibiting, activates bcl-xl
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Structure:
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Bcl-2-like protein 1,apoptosis regulator bcl-xl. Chain: a, b. Synonym: bcl2-l-1,apoptosis regulator bcl-x. Engineered: yes. Mutation: yes. Translationally-controlled tumor protein. Chain: c, d, e, f, g, h. Synonym: tctp,fortilin,histamine-releasing factor,hrf,p23. Engineered: yes.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: bcl2l1, bcl2l, bclx. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_cell_line: prare2. Gene: tpt1. Expression_system_taxid: 469008
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Resolution:
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2.10Å
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R-factor:
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0.187
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R-free:
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0.222
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Authors:
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V.Cura,M.Agez,S.Thebault,J.Cavarelli
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Key ref:
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S.Thébault
et al.
(2016).
TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL.
Sci Rep,
6,
19725.
PubMed id:
DOI:
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Date:
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12-Apr-15
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Release date:
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10-Feb-16
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PROCHECK
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Headers
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References
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Q07817
(B2CL1_HUMAN) -
Bcl-2-like protein 1 from Homo sapiens
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Seq:
Struc:
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233 a.a.
153 a.a.
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P13693
(TCTP_HUMAN) -
Translationally-controlled tumor protein from Homo sapiens
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Seq:
Struc:
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172 a.a.
15 a.a.
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P13693
(TCTP_HUMAN) -
Translationally-controlled tumor protein from Homo sapiens
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Seq:
Struc:
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172 a.a.
16 a.a.
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DOI no:
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Sci Rep
6:19725
(2016)
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PubMed id:
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TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL.
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S.Thébault,
M.Agez,
X.Chi,
J.Stojko,
V.Cura,
S.B.Telerman,
L.Maillet,
F.Gautier,
I.Billas-Massobrio,
C.Birck,
N.Troffer-Charlier,
T.Karafin,
J.Honoré,
A.Senff-Ribeiro,
S.Montessuit,
C.M.Johnson,
P.Juin,
S.Cianférani,
J.C.Martinou,
D.W.Andrews,
R.Amson,
A.Telerman,
J.Cavarelli.
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ABSTRACT
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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.
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