3ygs
APAF-1 CARD IN COMPLEX WITH PRODOMAIN OF PROCASPASE-9
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OverviewOverview
Caspase-9-mediated apoptosis (programmed cell death) plays a central role, in the development and homeostasis of all multicellular organisms. Mature, caspase-9 is derived from its procaspase precursor as a result of, recruitment by the activating factor Apaf-1. The crystal structures of the, caspase-recruitment domain of Apaf-1 by itself and in complex with the, prodomain of procaspase-9 have been determined at 1.6 and 2.5 A, resolution, respectively. These structures and other evidence reveal that, each molecule of Apaf-1 interacts with a molecule of procaspase-9 through, two highly charged and complementary surfaces formed by non-conserved, residues; these surfaces determine recognition specificity through, networks of intermolecular hydrogen bonds and van der Waals interactions., Mutation of the important interface residues in procaspase-9 or Apaf-1, prevents or reduces activation of procaspase-9 in a cell-free system., Wild-type, but not mutant, prodomains of caspase-9 completely inhibit, catalytic processing of procaspase-9. Furthermore, analysis of homologues, from Caenorhabditis elegans indicates that recruitment of CED-3 by CED-4, is probably mediated by the same set of conserved structural motifs, with, a corresponding change in the specificity-determining residues.
About this StructureAbout this Structure
3YGS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1., Qin H, Srinivasula SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y, Nature. 1999 Jun 10;399(6736):549-57. PMID:10376594
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