DARK apoptosome secrets come to light

Abstract

In this issue of Structure, Yuan et al. (2011) utilize biochemical approaches to reconstitute an active Drosophila apoptosome, as well as cryo-electron microscopy to generate an improved model for this conserved caspase-activating complex.

Figure 1. Models of the DARK Apoptosome Complex

(A) In the previous model of the DARK apoptosome, the CARDs were thought to form an inner ring, surrounded by alternating NBDs and winged-helix domains (WHDs). Helical domain I (HDI) sat atop the NBD, and helical domain II (HDII) extended from the WHD to two β-propellers. (B) In the current model, the NBDs form the inner ring and are encircled by a crown of CARDs. The CARDs are connected to (and make additional contacts with) the NBDs, but also rest near the adjacent β7 propellers. Thus, significant conformational changes are likely required to expose the CARDs and facilitate DRONC binding. Note, in this top view, the HDII rests beneath the CARD and is not visible.