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Updated: Jun 8, 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

Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation

Xiao-Jun Wang1, Qin Cao, Xiang Liu

  • 1National Laboratory of Protein Engineering & Plant Genetic Engineering, Peking University, Haidian District, Beijing, People's Republic of China.

EMBO Reports
|October 5, 2010
PubMed

Insights

Caspase 6 (CASP6) activation involves intramolecular self-cleavage. Structural and biochemical studies reveal CASP6 zymogen

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • Dimeric effector caspases (caspase 3 and 7) are activated via initiator caspase processing.
  • Caspase 6 (CASP6) is an effector caspase with a critical role in apoptosis.
  • Understanding CASP6 activation mechanisms is crucial for cellular regulation studies.

Purpose of the Study:

  • To determine the crystal structures of caspase 6 (CASP6) zymogen and an inhibited CASP6 form.
  • To elucidate the molecular mechanism of CASP6 auto-activation.
  • To investigate the role of intramolecular cleavage in CASP6 activation.

Main Methods:

  • X-ray crystallography to obtain high-resolution structures of CASP6 zymogen and inhibited CASP6.
  • Biochemical assays to assess CASP6 self-activation.
  • Analysis of the intersubunit cleavage site and its interaction with the active site.

Main Results:

  • Both CASP6 zymogen and inhibited forms adopt a dimeric structure.
  • The intersubunit cleavage site (190)TEVD(193) in CASP6 zymogen is structured to insert into the active site.
  • Intramolecular cleavage at Asp 193 is essential for CASP6 self-activation, a process influenced by L2 loop length.

Conclusions:

  • CASP6 activation is an intramolecular process.
  • Self-cleavage at Asp 193 is a prerequisite for CASP6 auto-activation.
  • The L2 loop length modulates CASP6 activation, highlighting a novel regulatory mechanism.

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