@article{93fed85f1ce04d51ac922763a0c62cd1,
title = "Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome",
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 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.",
author = "Su, {Tsung Wei} and Yang, {Chao Yu} and Kao, {Wen Pin} and Kuo, {Bai Jiun} and Lin, {Shan Meng} and Lin, {Jung Yaw} and Lo, {Yu Chih} and Lin, {Su Chang}",
note = "Funding Information: We thank the Mass Spectrometry and Protein X-ray Diffractometer facilities of Genomics Research Center, and the SIC Sequencing Core Facility, Academia Sinica (AS), Taiwan, for protein ID, crystallization screening, and DNA sequencing, respectively. We thank the technical services provided by the Synchrotron Radiation Protein Crystallography Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology and the NSRRC, a national user facility supported by the Ministry of Science and Technology, Taiwan, ROC. We also thank the support at the beamline BL23A1 at NSRRC, Taiwan, for the SAXS experiments, and BL44XU at SPring-8, Japan, for X-ray diffraction data collection. This work was supported by AS (AS-102-TP-B14-1 to Y.-C.L., AS-102-TP-B14 and AS-102-TP-B14-2 to S.-C.L., and AS Postdoctoral Fellowship to C.-Y.Y.), Ministry of Science and Technology (MoST) (NSC 101-2320-B-001-034-MY3 and MoST 104-2320-B-001-020-MY3 to S.-C.L.; NSC 101-2311-B-006-008-MY3 and MoST 104-2320-B-006-033-MY3 to Y.-C.L.), and National Taiwan Normal University (104T3040D0 to J.-Y.L.), Taiwan.",
year = "2017",
month = mar,
day = "7",
doi = "10.1016/j.str.2016.12.019",
language = "English",
volume = "25",
pages = "407--420",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "3",
}