A structure of the human apoptosome at 12.8 A resolution provides insights into this cell death platform |
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Authors: | Yu Xinchao Acehan Devrim Ménétret Jean-François Booth Christopher R Ludtke Steven J Riedl Stefan J Shi Yigong Wang Xiaodong Akey Christopher W |
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Institution: | Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA. |
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Abstract: | Apaf-1 and cytochrome c coassemble in the presence of dATP to form the apoptosome. We have determined a structure of the apoptosome at 12.8 A resolution by using electron cryomicroscopy and single-particle methods. We then docked appropriate crystal structures into the map to create an accurate domain model. Thus, we found that seven caspase recruitment domains (CARDs) form a central ring within the apoptosome. At a larger radius, seven copies of the nucleotide binding and oligomerization domain (NOD) associate laterally to form the hub, which encircles the CARD ring. Finally, an arm-like helical domain (HD2) links each NOD to a pair of beta propellers, which bind a single cytochrome c. This model provides insights into the roles of dATP and cytochrome c in assembly. Our structure also reveals how a CARD ring and the central hub combine to create a platform for procaspase-9 activation. |
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