4RHW

Crystal structure of Apaf-1 CARD and caspase-9 CARD complex

Summary for 4RHW

• Entry DOI: 10.2210/pdb4rhw/pdb
• Descriptor: Apoptotic protease-activating factor 1, Caspase-9, SULFATE ION, ... (5 entities in total)
• Functional Keywords: death domain superfamily, apoptosis
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 70625.29

Authors

Hu, Q.,Wu, D.,Yan, C.,Shi, Y. (deposition date: 2014-10-03, release date: 2014-10-15, Last modification date: 2023-11-08)

Primary citation

Hu, Q.,Wu, D.,Chen, W.,Yan, Z.,Yan, C.,He, T.,Liang, Q.,Shi, Y.
Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome.
Proc. Natl. Acad. Sci. U.S.A., 111:16254-16261, 2014

PubMed Abstract: Autocatalytic activation of an initiator caspase triggers the onset of apoptosis. In dying cells, caspase-9 activation is mediated by a multimeric adaptor complex known as the Apaf-1 apoptosome. The molecular mechanism by which caspase-9 is activated by the Apaf-1 apoptosome remains largely unknown. Here we demonstrate that the previously reported 1:1 interaction between Apaf-1 caspase recruitment domain (CARD) and caspase-9 CARD is insufficient for the activation of caspase-9. Rather, formation of a multimeric CARD:CARD assembly between Apaf-1 and caspase-9, which requires three types of distinct interfaces, underlies caspase-9 activation. Importantly, an additional surface area on the multimeric CARD assembly is essential for caspase-9 activation. Together, these findings reveal mechanistic insights into the activation of caspase-9 by the Apaf-1 apoptosome and support the induced conformation model for initiator caspase activation by adaptor complexes.

PubMed: 25313070
DOI: 10.1073/pnas.1418000111

Experimental method

X-RAY DIFFRACTION (2.1 Å)