PDBsum entry 5wvc

Apoptosis

PDB id: 5wvc

Contents

Protein chains

95 a.a.

103 a.a.

Metals

IOD ×11

PDB id:

5wvc

Name:

Apoptosis

Title:

Structure of the card-card disk

Structure:

Apoptotic protease-activating factor 1. Chain: c, a, e. Fragment: unp residues 1-95. Synonym: apaf-1. Engineered: yes. Caspase. Chain: d, b, f. Fragment: unp residues 1-128. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: apaf1, kiaa0413. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Resolution:

2.99Å R-factor: 0.199 R-free: 0.228

Authors:

S.C.Lin,Y.C.Lo,T.W.Su

Key ref:

T.W.Su et al. (2017). Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome. Structure, 25, 407-420. PubMed id: 28111022

Date:

24-Dec-16 Release date: 19-Apr-17

Protein chains

O14727  (APAF_HUMAN) -  Apoptotic protease-activating factor 1 from Homo sapiens

Seq: 1248 a.a.

Struc: 95 a.a.

Protein chains

P55211  (CASP9_HUMAN) -  Caspase-9 from Homo sapiens

Seq: 416 a.a.

Struc: 103 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains D, B, F: E.C.3.4.22.62 - caspase-9.

Structure 25:407-420 (2017)

PubMed id: 28111022

Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.

T.W.Su, C.Y.Yang, W.P.Kao, B.J.Kuo, S.M.Lin, J.Y.Lin, Y.C.Lo, S.C.Lin.

ABSTRACT

Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly.