[HTML][HTML] Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation

D Acehan, X Jiang, DG Morgan, JE Heuser, X Wang… - Molecular cell, 2002 - cell.com
D Acehan, X Jiang, DG Morgan, JE Heuser, X Wang, CW Akey
Molecular cell, 2002cell.com
The apoptosome is an Apaf-1 cytochrome c complex that activates procaspase-9. The three-
dimensional structure of the apoptosome has been determined at 27 Å resolution, to reveal
a wheel-like particle with 7-fold symmetry. Molecular modeling was used to identify the
caspase recruitment and WD40 domains within the apoptosome and to infer likely positions
of the CED4 homology motif and cytochrome c. This analysis suggests a plausible role for
cytochrome c in apoptosome assembly. In a subsequent structure, a noncleavable mutant of …
Abstract
The apoptosome is an Apaf-1 cytochrome c complex that activates procaspase-9. The three-dimensional structure of the apoptosome has been determined at 27 Å resolution, to reveal a wheel-like particle with 7-fold symmetry. Molecular modeling was used to identify the caspase recruitment and WD40 domains within the apoptosome and to infer likely positions of the CED4 homology motif and cytochrome c. This analysis suggests a plausible role for cytochrome c in apoptosome assembly. In a subsequent structure, a noncleavable mutant of procaspase-9 was localized to the central region of the apoptosome. This complex promotes the efficient activation of procaspase-3. Therefore, the cleavage of procaspase-9 is not required to form an active cell death complex.
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