3J9L
Structure of Dark apoptosome from Drosophila melanogaster
This is a non-PDB format compatible entry.
Summary for 3J9L
| Entry DOI | 10.2210/pdb3j9l/pdb |
| Related | 3J9K |
| EMDB information | 2870 2871 |
| Descriptor | Apaf-1 related killer DARK, 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE (2 entities in total) |
| Functional Keywords | programmed cell death, apoptosis |
| Biological source | Drosophila melanogaster (Fruit fly) |
| Total number of polymer chains | 16 |
| Total formula weight | 1812715.99 |
| Authors | |
| Primary citation | Pang, Y.,Bai, X.C.,Yan, C.,Hao, Q.,Chen, Z.,Wang, J.W.,Scheres, S.H.,Shi, Y. Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila. Genes Dev., 29:277-287, 2015 Cited by PubMed Abstract: Apoptosis is executed by a cascade of caspase activation. The autocatalytic activation of an initiator caspase, exemplified by caspase-9 in mammals or its ortholog, Dronc, in fruit flies, is facilitated by a multimeric adaptor complex known as the apoptosome. The underlying mechanism by which caspase-9 or Dronc is activated by the apoptosome remains unknown. Here we report the electron cryomicroscopic (cryo-EM) structure of the intact apoptosome from Drosophila melanogaster at 4.0 Å resolution. Analysis of the Drosophila apoptosome, which comprises 16 molecules of the Dark protein (Apaf-1 ortholog), reveals molecular determinants that support the assembly of the 2.5-MDa complex. In the absence of dATP or ATP, Dronc zymogen potently induces formation of the Dark apoptosome, within which Dronc is efficiently activated. At 4.1 Å resolution, the cryo-EM structure of the Dark apoptosome bound to the caspase recruitment domain (CARD) of Dronc (Dronc-CARD) reveals two stacked rings of Dronc-CARD that are sandwiched between two octameric rings of the Dark protein. The specific interactions between Dronc-CARD and both the CARD and the WD40 repeats of a nearby Dark protomer are indispensable for Dronc activation. These findings reveal important mechanistic insights into the activation of initiator caspase by the apoptosome. PubMed: 25644603DOI: 10.1101/gad.255877.114 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4 Å) |
Structure validation
Download full validation report
