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Caspase-9 CARD : core domain interactions require a properly formed active site

Kristen L Huber, Banyuhay P Serrano, Jeanne A Hardy1

  • 1Department of Chemistry, 104 LGRT, 710 N. Pleasant St, University of Massachusetts, Amherst, MA 01003, U.S.A. hardy@chem.umass.edu.

The Biochemical Journal
|March 4, 2018
PubMed

Insights

The caspase-9 CARD domain interacts with its catalytic core, revealing a new regulatory mechanism. This interaction depends on an ordered active site, suggesting novel roles beyond apoptosome recruitment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Caspase-9 is a key regulator of apoptosis, essential for programmed cell death.
  • Its Caspase Activation and Recruitment Domain (CARD) facilitates interaction with the apoptosome.
  • The precise function of the caspase-9 CARD outside of apoptosome interaction remains largely unexplored.

Purpose of the Study:

  • To investigate the role of the caspase-9 CARD domain in regulating caspase-9 activity.
  • To explore potential interactions of the CARD domain independent of the apoptosome.
  • To elucidate the structural requirements for CARD-core domain interaction.

Main Methods:

  • Biochemical assays to study protein-protein interactions.
  • Analysis of caspase-9 structure and active site dynamics.
  • Investigating the impact of active site conformation on CARD-core interaction.

Main Results:

  • The caspase-9 CARD domain physically interacts with the catalytic core of caspase-9.
  • This interaction is dependent on a properly formed and ordered active site.
  • Disordered active site loops prevent CARD-core interaction, leading to independent domain behavior.

Conclusions:

  • The caspase-9 CARD domain plays a regulatory role through intramolecular interaction with the catalytic core.
  • Active site conformation is critical for this novel regulatory mechanism.
  • The CARD domain may be involved in substrate recruitment or recognition in addition to apoptosome binding.

Keywords:
CARDapoptosiscaspase-9circular dichroisminterdomain interactionsprotein conformation

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