2YGS

CARD DOMAIN FROM APAF-1

Summary for 2YGS

• Entry DOI: 10.2210/pdb2ygs/pdb
• Related: 3YGS
• Descriptor: APOPTOTIC PROTEASE ACTIVATING FACTOR 1 (2 entities in total)
• Functional Keywords: apoptosis, caspase recruitment domain, apaf-1, recognition
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O14727
• Total number of polymer chains: 1
• Total formula weight: 10640.22

Authors

Shi, Y. (deposition date: 1999-05-08, release date: 2000-04-19, Last modification date: 2023-12-27)

Primary citation

Qin, H.,Srinivasula, S.M.,Wu, G.,Fernandes-Alnemri, T.,Alnemri, E.S.,Shi, Y.
Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1.
Nature, 399:549-557, 1999

PubMed Abstract: 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.

PubMed: 10376594
DOI: 10.1038/21124

Experimental method

X-RAY DIFFRACTION (1.6 Å)