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Updated: Jun 22, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment

J J Chou1, H Matsuo, H Duan

  • 1Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA.

Cell
|August 8, 1998
PubMed

Insights

The caspase recruitment domain (CARD) structure of RAIDD reveals a conserved surface polarity. This polarity is crucial for CARD/CARD interactions, mediating caspase recruitment during apoptosis.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Cell Death Pathways

Background:

  • Apoptosis (programmed cell death) involves the recruitment of caspases by adaptor proteins via homophilic interactions.
  • These interactions occur between caspase recruitment domains (CARDs) of adaptors and the prodomains of caspases.

Purpose of the Study:

  • To determine the three-dimensional structure of the RAIDD adaptor protein's CARD.
  • To elucidate the molecular mechanism of CARD/CARD interactions in caspase recruitment.

Main Methods:

  • X-ray crystallography was used to solve the CARD structure of the RAIDD adaptor protein.
  • Homology modeling was employed to predict the structure of the ICH-1 CARD.
  • Mutagenesis studies were performed to investigate the role of surface patches in CARD/CARD interactions.

Main Results:

  • The RAIDD CARD structure comprises six helices, topologically similar to the Fas death domain.
  • The RAIDD CARD surface exhibits distinct basic and acidic patches.
  • These surface polarities are conserved in the ICH-1 CARD and mediate interactions between RAIDD and ICH-1.

Conclusions:

  • The solved structure of the RAIDD CARD provides insights into the molecular basis of caspase recruitment.
  • A conserved basic/acidic surface polarity in CARDs appears to be a general mechanism for CARD/CARD interactions.
  • This mechanism is likely fundamental for the function of various apoptosis-related proteins, including Apaf-1, caspase-9, Ced-4, and Ced-3.

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