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TitleAtomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1.
Journal, issue, pagesGenes Dev, Vol. 29, Issue 22, Page 2349-2361, Year 2015
Publish dateNov 15, 2015
AuthorsMengying Zhou / Yini Li / Qi Hu / Xiao-Chen Bai / Weiyun Huang / Chuangye Yan / Sjors H W Scheres / Yigong Shi /
PubMed AbstractThe 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 ...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.
External linksGenes Dev / PubMed:26543158 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 4.4 Å
Structure data

6480

3jbt

EMDB-6480, PDB-3jbt:
Atomic structure of the Apaf-1 apoptosome
Method: EM (single particle) / Resolution: 3.8 Å

6481

3jbt

EMDB-6481, PDB-3jbt:
Atomic structure of the Apaf-1 apoptosome
Method: EM (single particle) / Resolution: 4.4 Å

Chemicals

ChemComp-DTP:
2'-DEOXYADENOSINE 5'-TRIPHOSPHATE

ChemComp-MG:
Unknown entry

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE

Source
  • homo sapiens (human)
  • equus caballus (horse)
KeywordsAPOPTOSIS / Apoptosome / cryo-EM structure / Apaf-1

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