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TitleA near atomic structure of the active human apoptosome.
Journal, issue, pagesElife, Vol. 5, Year 2016
Publish dateOct 4, 2016
AuthorsTat Cheung Cheng / Chuan Hong / Ildikó V Akey / Shujun Yuan / Christopher W Akey /
PubMed AbstractIn 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- ...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.
External linksElife / PubMed:27697150 / PubMed Central
MethodsEM (single particle)
Resolution4.1 Å
Structure data

8178

5juy

EMDB-8178, PDB-5juy:
Active human apoptosome with procaspase-9
Method: EM (single particle) / Resolution: 4.1 Å

Chemicals

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

ChemComp-HEC:
HEME C

Source
  • homo sapiens (human)
  • Bovine (cattle)
  • bos taurus (cattle)
KeywordsAPOPTOSIS / Apaf-1 / programmed cell death / AAA+ ATPase

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