5jul

Publication Abstract from PubMed

In Drosophila, the Apaf-1-related killer (Dark) forms an apoptosome that activates procaspases. To investigate function, we have determined a near-atomic structure of Dark double rings using cryo-electron microscopy. We then built a nearly complete model of the apoptosome that includes 7- and 8-blade beta-propellers. We find that the preference for dATP during Dark assembly may be governed by Ser325, which is in close proximity to the 2' carbon of the deoxyribose ring. Interestingly, beta-propellers in V-shaped domains of the Dark apoptosome are more widely separated, relative to these features in the Apaf-1 apoptosome. This wider spacing may be responsible for the lack of cytochrome c binding to beta-propellers in the Dark apoptosome. Our structure also highlights the roles of two loss-of-function mutations that may block Dark assembly. Finally, the improved model provides a framework to understand apical procaspase activation in the intrinsic cell death pathway.

A Near-Atomic Structure of the Dark Apoptosome Provides Insight into Assembly and Activation.,Cheng TC, Akey IV, Yuan S, Yu Z, Ludtke SJ, Akey CW Structure. 2017 Jan 3;25(1):40-52. doi: 10.1016/j.str.2016.11.002. Epub 2016 Dec , 1. PMID:27916517^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.