A near atomic structure of the active human apoptosome.

Abstract:

:In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease.

journal_name

Elife

journal_title

eLife

authors

Cheng TC,Hong C,Akey IV,Yuan S,Akey CW

doi

10.7554/eLife.17755

subject

Has Abstract

pub_date

2016-10-04 00:00:00

issn

2050-084X

journal_volume

5

pub_type

杂志文章

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