Tumor cells or virally infected cells are a danger to our lifes, but fortunately killer cells of the immune defense system which are armed with different specialized digestive enzymes, called granzymes, eradicate these cells in many instances. The granzymes A and B, two of these proteases, are highly efficient triggers of intracellular cell death inducing (cytotoxic) cascades. The same beneficial effector molecules, however, can also turn their powerful energies against transplanted organs, grafted stem cells and self-tissues in autoimmune disorders and are then detrimental and life-theatening to the patients. Among the 120 different serine proteases of the human genome, granzyme A is a unique double-headed protease (homodimer) with two identical catalytic domains connected by a covalent disulfide bond. Clara Hink-Schauer, Eva Estebanez-Perpina, Florian Kurschus, Wolfram Bode and Dieter E. Jenne from the Max Planck Institutes of Biochemistry and Neurobiology, Martinsried near Munich, Germany, have now uncovered the secret of this tandem configuration by analyzing the three-dimensional structure of granzyme A at 2.5 Å resolution (Nature Structural Biology 10, 535-540, July 2003).
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