3JBT

Atomic structure of the Apaf-1 apoptosome

Summary for 3JBT

• Entry DOI: 10.2210/pdb3jbt/pdb
• EMDB information: 6480
• Descriptor: Apoptotic protease-activating factor 1, Cytochrome c, 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: apoptosome, cryo-em structure, apoptosis, apaf-1
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 14
• Total formula weight: 1096452.78

Authors

Zhou, M.,Li, Y.,Hu, Q.,Bai, X.,Huang, W.,Yan, C.,Scheres, S.H.W.,Shi, Y. (deposition date: 2015-10-15, release date: 2015-11-18, Last modification date: 2024-11-20)

Primary citation

Zhou, M.,Li, Y.,Hu, Q.,Bai, X.C.,Huang, W.,Yan, C.,Scheres, S.H.W.,Shi, Y.
Atomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1
Genes Dev., 29:2349-2361, 2015

PubMed Abstract: The apoptotic protease-activating factor 1 (Apaf-1) controls the onset of many known forms of intrinsic apoptosis in mammals. Apaf-1 exists in normal cells as an autoinhibited monomer. Upon binding to cytochrome c and dATP, Apaf-1 oligomerizes into a heptameric complex known as the apoptosome, which recruits and activates cell-killing caspases. Here we present an atomic structure of an intact mammalian apoptosome at 3.8 Å resolution, determined by single-particle, cryo-electron microscopy (cryo-EM). Structural analysis, together with structure-guided biochemical characterization, uncovered how cytochrome c releases the autoinhibition of Apaf-1 through specific interactions with the WD40 repeats. Structural comparison with autoinhibited Apaf-1 revealed how dATP binding triggers a set of conformational changes that results in the formation of the apoptosome. Together, these results constitute the molecular mechanism of cytochrome c- and dATP-mediated activation of Apaf-1.

PubMed: 26543158
DOI: 10.1101/gad.272278.115

Experimental method

ELECTRON MICROSCOPY (3.8 Å)