Unknown

Dataset Information

0

The holo-apoptosome: activation of procaspase-9 and interactions with caspase-3.


ABSTRACT: Activation of procaspase-9 on the apoptosome is a pivotal step in the intrinsic cell death pathway. We now provide further evidence that caspase recruitment domains of pc-9 and Apaf-1 form a CARD-CARD disk that is flexibly tethered to the apoptosome. In addition, a 3D reconstruction of the pc-9 apoptosome was calculated without symmetry restraints. In this structure, p20 and p10 catalytic domains of a single pc-9 interact with nucleotide binding domains of adjacent Apaf-1 subunits. Together, disk assembly and pc-9 binding create an asymmetric proteolysis machine. We also show that CARD-p20 and p20-p10 linkers play important roles in pc-9 activation. Based on the data, we propose a proximity-induced association model for pc-9 activation on the apoptosome. We also show that pc-9 and caspase-3 have overlapping binding sites on the central hub. These binding sites may play a role in pc-3 activation and could allow the formation of hybrid apoptosomes with pc-9 and caspase-3 proteolytic activities.

SUBMITTER: Yuan S 

PROVIDER: S-EPMC3155825 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3644875 | BioStudies
2013-01-01 | S-EPMC3645920 | BioStudies
2010-01-01 | S-EPMC2874686 | BioStudies
2016-01-01 | S-EPMC5050015 | BioStudies
2018-01-01 | S-EPMC6030056 | BioStudies
2017-01-01 | S-EPMC5530255 | BioStudies
2014-01-01 | S-EPMC4246342 | BioStudies
2017-01-01 | S-EPMC5320974 | BioStudies
1000-01-01 | S-EPMC4285429 | BioStudies
2015-01-01 | S-EPMC4318144 | BioStudies