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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Human and murine granzyme B exhibit divergent substrate preferences
Sean P Cullen1, Colin Adrain, Alexander U Lüthi
1Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
The Journal of Cell Biology
|February 7, 2007
Summary
Human and mouse granzyme B (GzmB) proteases show distinct substrate preferences, impacting apoptosis pathways differently. Subtle structural variations significantly alter GzmB
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Cytotoxic lymphocyte protease granzyme B (GzmB) induces apoptosis via caspase activation and mitochondrial permeabilization.
- Human and mouse GzmB share homology but differ in residues affecting substrate binding.
Purpose of the Study:
- To investigate the functional differences between human and mouse granzyme B (GzmB).
- To determine how structural variations influence GzmB substrate specificity and apoptotic function.
Main Methods:
- Comparative analysis of human and mouse GzmB substrate cleavage.
- Assessment of caspase-dependent and -independent apoptosis pathways.
- Pharmacological inhibition of caspases to evaluate cell rescue.
Main Results:
- Human and mouse GzmB exhibit significant differences in cleaving key substrates like BID, ICAD, and caspase-8.
- Caspase inhibition rescued cells from mouse GzmB-induced apoptosis but not human GzmB-induced apoptosis.
- These findings highlight divergent substrate specificities between human and murine GzmB.
Conclusions:
- Human and mouse granzyme B are distinct enzymes with unique substrate preferences.
- Minor structural differences in GzmB can lead to major functional and substrate selection variations.
- Understanding these differences is crucial for targeted therapeutic strategies involving GzmB.
