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Related Experiment Videos

Structural basis for the activation of human procaspase-7.

S J Riedl1, P Fuentes-Prior, M Renatus

  • 1Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany. riedl@biochem.mpg.de

Proceedings of the National Academy of Sciences of the United States of America
|December 26, 2001
PubMed
Summary

This study reveals the three-dimensional structure of inactive procaspase-7, detailing how its activation mechanism differs from other proteinase zymogens. Understanding caspase activation is key to apoptosis research.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Caspases are crucial proteinases in apoptosis, with initiator caspases activating executioner caspases via proteolytic cleavage.
  • While active caspase structures are known, the three-dimensional structure of uncleaved caspase zymogens remained elusive.

Purpose of the Study:

  • To determine the crystal structure of recombinant human C285A procaspase-7.
  • To elucidate the activation mechanism of caspases at a structural level.

Main Methods:

  • Determined the 2.9-Å crystal structure of recombinant human C285A procaspase-7.
  • Analyzed the structural differences between procaspase-7 and active caspase-7.

Main Results:

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  • The homodimeric procaspase-7 structure resembles active tetrameric caspase-7, with flexible linkers blocking the active site cavity.
  • Proteolytic cleavage within these linkers allows termini to move, forming a functional active-site cleft.
  • This represents a novel mechanism for proteinase zymogen activation.

    • Conclusions:

    • The structural data provides unprecedented insight into the activation mechanism of caspases.
    • This finding reveals a previously unknown mode of proteinase zymogen activation, distinct from other known pathways.