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PDBsum entry 1c15
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure of apaf-1 card and its interaction with caspase-9 card: a structural basis for specific adaptor/caspase interaction.
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Authors
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P.Zhou,
J.Chou,
R.S.Olea,
J.Yuan,
G.Wagner.
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Ref.
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Proc Natl Acad Sci U S A, 1999,
96,
11265-11270.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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).
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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.
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