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Publication Abstract from PubMed

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 1:1 Apaf-1:procaspase-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.

Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.,Su TW, Yang CY, Kao WP, Kuo BJ, Lin SM, Lin JY, Lo YC, Lin SC Structure. 2017 Mar 7;25(3):407-420. doi: 10.1016/j.str.2016.12.019. Epub 2017, Jan 19. PMID:28111022^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.