Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.
Structure
; 25(3): 407-420, 2017 03 07.
Article
in En
| MEDLINE
| ID: mdl-28111022
ABSTRACT
Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 11 Apaf-1procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apoptosomes
/
Caspase 9
/
Apoptotic Protease-Activating Factor 1
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Structure
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Year:
2017
Document type:
Article
Affiliation country: