TY - JOUR TI - A near atomic structure of the active human apoptosome AU - Cheng, Tat Cheung AU - Hong, Chuan AU - Akey, Ildikó V AU - Yuan, Shujun AU - Akey, Christopher W A2 - Subramaniam, Sriram VL - 5 PY - 2016 DA - 2016/10/04 SP - e17755 C1 - eLife 2016;5:e17755 DO - 10.7554/eLife.17755 UR - https://doi.org/10.7554/eLife.17755 AB - In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease. KW - apoptosome KW - programmed cell death KW - procaspase-9 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -