5JUL

Near atomic structure of the Dark apoptosome

This is a non-PDB format compatible entry.

Summary for 5JUL

• Entry DOI: 10.2210/pdb5jul/pdb
• EMDB information: 8177
• Descriptor: Apaf-1 related killer DARK, 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE (2 entities in total)
• Functional Keywords: dark, apoptosome, apotosis, aaa+ atpase, apoptosis
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 16
• Total formula weight: 2665954.91

Authors

Cheng, T.C.,Akey, I.V.,Yuan, S.,Yu, Z.,Ludtke, S.J.,Akey, C.W. (deposition date: 2016-05-10, release date: 2017-02-22, Last modification date: 2019-12-25)

Primary citation

Cheng, T.C.,Akey, I.V.,Yuan, S.,Yu, Z.,Ludtke, S.J.,Akey, C.W.
A Near-Atomic Structure of the Dark Apoptosome Provides Insight into Assembly and Activation.
Structure, 25:40-52, 2017

PubMed Abstract: 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 β-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, β-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 β-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.

PubMed: 27916517
DOI: 10.1016/j.str.2016.11.002

Experimental method

ELECTRON MICROSCOPY (4.4 Å)