title: Structure of the Drosophila apoptosome at 6.9 å resolution.
abstract: The Drosophila Apaf-1 related killer forms an apoptosome in the intrinsic cell death pathway. In this study we show that Dark forms a single ring when initiator procaspases are bound. This Dark-Dronc complex cleaves DrICE efficiently; hence, a single ring represents the Drosophila apoptosome. We then determined the 3D structure of a double ring at ∼6.9 Å resolution and created a model of the apoptosome. Subunit interactions in the Dark complex are similar to those in Apaf-1 and CED-4 apoptosomes, but there are significant differences. In particular, Dark has "lost" a loop in the nucleotide-binding pocket, which opens a path for possible dATP exchange in the apoptosome. In addition, caspase recruitment domains (CARDs) form a crown on the central hub of the Dark apoptosome. This CARD geometry suggests that conformational changes will be required to form active Dark-Dronc complexes. When taken together, these data provide insights into apoptosome structure, function, and evolution.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA.
authors.forename: Shujun
authors.initials: S
authors.lastname: Yuan
authors.forename: Xinchao
authors.initials: X
authors.lastname: Yu
authors.forename: Maya
authors.initials: M
authors.lastname: Topf
authors.forename: Loretta
authors.initials: L
authors.lastname: Dorstyn
authors.forename: Sharad
authors.initials: S
authors.lastname: Kumar
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ludtke
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Akey
mesh_terms: D000818:Animals; D053478:Apoptosomes / Q000737:chemistry*; D020169:Caspases / Q000737:chemistry*; D020285:Cryoelectron Microscopy; D029721:Drosophila Proteins / Q000737:chemistry*; D004331:Drosophila melanogaster / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: D053478:Apoptosomes; D029721:Drosophila Proteins; C400550:dark protein, Drosophila; D020169:Caspases; C109171:drICE protein, Drosophila; C118731:dronc protein, Drosophila