A near-atomic structure of the dark apoptosome provides insight into assembly and activation.

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Structure (London, England : 1993). 2016 Nov 16;25(1):40-52. doi: 10.1016/j.str.2016.11.002

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A near-atomic structure of the dark apoptosome provides insight into assembly and activation. Cryo-Electron Microscopy

Cheng TC, Akey IV, Yuan S, Yu Z, Ludtke SJ, Akey CW

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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.

PMID: 27916517 [PubMed - indexed for MEDLINE]

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A near-atomic structure of the dark apoptosome provides insight into assembly and activation.

Abstract

PMID: 27916517 [PubMed - indexed for MEDLINE]

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