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Related Experiment Video

Updated: Jul 18, 2026

A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl

A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl

Published on: November 28, 2014

The major human and mouse granzymes are structurally and functionally divergent.

Dion Kaiserman¹, Catherina H Bird, Jiuru Sun

¹Department of Biochemistry and Molecular Biology and 2Victorian Bioinformatics Consortium, Monash University, Victoria 3800, Australia.

The Journal of Cell Biology

|November 23, 2006

Summary

Mammalian granzymes, key immune proteases, evolve diverse functions. Mouse and human granzyme B and A show distinct cytotoxic activities, highlighting species-specific adaptations in immune defense evolution.

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Area of Science:

Immunology
Protease biochemistry
Comparative genomics

Background:

Proteases constitute ~2% of mammalian genes, with immune and reproductive proteases showing high evolutionary diversity.
Granzymes, cytotoxic proteases in natural killer cells and CD8+ T cells, are crucial for adaptive immunity.
Human and mouse genomes differ in granzyme gene counts (5 in humans, 10 in mice), suggesting evolutionary divergence.

Purpose of the Study:

To investigate the functional and structural differences between human and mouse granzymes.
To understand the evolutionary adaptations of granzymes in response to species-specific immune challenges.

Main Methods:

Comparative genomics analysis of granzyme gene families.
Biochemical characterization of human and mouse granzyme B and A.
Enzymatic activity assays and cytotoxicity measurements.
Site-directed mutagenesis to engineer active site clefts.

Main Results:

Mouse granzyme B exhibits 30-fold lower cytotoxicity than human granzyme B and functions independently of Bid.
Engineering the active site cleft of mouse granzyme B restores its cytotoxicity.
Mouse granzyme A demonstrates significantly higher cytotoxicity compared to human granzyme A.

Conclusions:

Granzymes, despite being orthologous, possess species-specific functions shaped by distinct evolutionary pressures.
Functional divergence in granzymes reflects adaptations to unique environmental challenges and immune system requirements.
Gene duplication and alterations in substrate specificity are key mechanisms driving granzyme evolution.