PDBsum entry 1c15

Apoptosis

PDB id: 1c15

Contents

Protein chain

97 a.a. *

* Residue conservation analysis

PDB id:

1c15

Name:

Apoptosis

Title:

Solution structure of apaf-1 card

Structure:

Apoptotic protease activating factor 1. Chain: a. Fragment: caspase recruitment domain. Synonym: apaf-1 card. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

16 models

Authors:

P.Zhou,J.Chou,R.S.Olea,J.Yuan,G.Wagner

Key ref:

P.Zhou et al. (1999). Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: a structural basis for specific adaptor/caspase interaction. Proc Natl Acad Sci U S A, 96, 11265-11270. PubMed id: 10500165 DOI: 10.1073/pnas.96.20.11265

Date:

20-Jul-99 Release date: 20-Sep-99

Protein chain

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

Seq: 1248 a.a.

Struc: 97 a.a.

DOI no: 10.1073/pnas.96.20.11265

Proc Natl Acad Sci U S A 96:11265-11270 (1999)

PubMed id: 10500165

Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: a structural basis for specific adaptor/caspase interaction.

P.Zhou, J.Chou, R.S.Olea, J.Yuan, G.Wagner.

ABSTRACT

Direct recruitment and activation of caspase-9 by Apaf-1 through the homophilic CARD/CARD (Caspase Recruitment Domain) interaction is critical for the activation of caspases downstream of mitochondrial damage in apoptosis. Here we report the solution structure of the Apaf-1 CARD domain and its surface of interaction with caspase-9 CARD. Apaf-1 CARD consists of six tightly packed amphipathic alpha-helices and is topologically similar to the RAIDD CARD, with the exception of a kink observed in the middle of the N-terminal helix. By using chemical shift perturbation data, the homophilic interaction was mapped to the acidic surface of Apaf-1 CARD centered around helices 2 and 3. Interestingly, a significant portion of the chemically perturbed residues are hydrophobic, indicating that in addition to the electrostatic interactions predicted previously, hydrophobic interaction is also an important driving force underlying the CARD/CARD interaction. On the basis of the identified functional residues of Apaf-1 CARD and the surface charge complementarity, we propose a model of CARD/CARD interaction between Apaf-1 and caspase-9.

Selected figure(s)

Figure 1.
Fig. 1. Solution structure of Apaf-1 CARD resembles other homophilic interacting motifs in apoptosis. (A) Stereoview of the backbone atoms (N, C^ , C') of the 15 superimposed NMR-derived structures of Apaf-1 CARD. The helices are numbered 1- 6 accordingly. (B-E) Ribbon diagrams of Apaf-1 CARD shown in red (B), RAIDD CARD in pink (C), FADD DED in dark blue (D), and Fas DD in green (E), illustrating the conserved six-helix bundle motif as well as variations of helix orientations among different domains. The coordinates of RAIDD CARD, FADD DED, and Fas DD were obtained from the Protein Data Bank (accession codes 3crd, 1a1w, and 1ddf).

Figure 3.
Fig. 3. Models of the Apaf-1/caspase-9 CARD complex. (A) Model of Apaf-1 CARD/caspase-9 CARD binary complex. Apaf-1 CARD is colored in pink, whereas caspase-9 CARD is colored in brown. The structure of caspase-9 CARD is constructed based on homology modeling of Apaf-1 CARD by using segment matching method (33). (B) Ribbon representation of caspase-9 CARD. The acidic, basic, and hydrophobic residues of 1 and 4 are colored in red, blue, and yellow, respectively. (C) Surface diagram of caspase-9 CARD in the same orientation as in B. In this figure, the surface electrostatic potential is color coded such that regions with electrostatic potentials < 8 k[BT] are red, whereas those >+8 k[BT] are blue (where k[B] and T are the Boltzmann constant and temperature, respectively). Surface-exposed hydrophobic residues are labeled in black.

Figures were selected by the author.