A structure of the human apoptosome at 12.8 A resolution provides insights into this cell death platform.
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.
Yu
Xinchao
X
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Acehan
Devrim
D
Ménétret
Jean-François
JF
Booth
Christopher R
CR
Ludtke
Steven J
SJ
Riedl
Stefan J
SJ
Shi
Yigong
Y
Wang
Xiaodong
X
Akey
Christopher W
CW
D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1 / Q000737:chemistry* / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D018360:Crystallography, X-Ray; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism; D003838:Deoxyadenine Nucleotides / Q000378:metabolism*; D006801:Humans; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein
D053477:Apoptotic Protease-Activating Factor 1; D003838:Deoxyadenine Nucleotides; D045304:Cytochromes c; D053453:Caspase 9