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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.

Publication ,  Journal Article
Zhou, P; Chou, J; Olea, RS; Yuan, J; Wagner, G
Published in: Proc Natl Acad Sci U S A
September 28, 1999

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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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 28, 1999

Volume

96

Issue

20

Start / End Page

11265 / 11270

Location

United States

Related Subject Headings

  • Proteins
  • Molecular Sequence Data
  • Models, Molecular
  • Magnetic Resonance Spectroscopy
  • Humans
  • Caspases
  • Caspase 9
  • Apoptotic Protease-Activating Factor 1
  • Amino Acid Sequence
 

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Zhou, P., Chou, J., Olea, R. S., Yuan, J., & Wagner, G. (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(20), 11265–11270. https://doi.org/10.1073/pnas.96.20.11265
Zhou, P., J. Chou, R. S. Olea, J. Yuan, and G. Wagner. “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, no. 20 (September 28, 1999): 11265–70. https://doi.org/10.1073/pnas.96.20.11265.
Zhou P, Chou J, Olea RS, Yuan J, Wagner G. 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. 1999 Sep 28;96(20):11265–70.
Zhou, P., et al. “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, vol. 96, no. 20, Sept. 1999, pp. 11265–70. Pubmed, doi:10.1073/pnas.96.20.11265.
Zhou P, Chou J, Olea RS, Yuan J, Wagner G. 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. 1999 Sep 28;96(20):11265–11270.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 28, 1999

Volume

96

Issue

20

Start / End Page

11265 / 11270

Location

United States

Related Subject Headings

  • Proteins
  • Molecular Sequence Data
  • Models, Molecular
  • Magnetic Resonance Spectroscopy
  • Humans
  • Caspases
  • Caspase 9
  • Apoptotic Protease-Activating Factor 1
  • Amino Acid Sequence