“We have identified a new family of enzymes. One of these enzymes, Rpn11, is essential for the protein-degrading activity of a large cellular "machine" known as the proteasome.”

Perhaps the best way to answer this question is by analogy. If somebody were to give you a computer and tell you that it uses strings of 1's and 0's to carry out computations, you would be hard-pressed to build productively upon that knowledge. Imagine, however, that someone gave you the computer, an operating system, and source code for the operating system. Armed with that information plus some familiarity with computer programming, you could develop simple software applications to run on the computer. All of a sudden the computer has been transformed from an abstract idea to a useful device that others can build upon. Our discovery of the JAMM motif and demonstration that it specifies a metalloprotease activity constitute, in essence, "source code" for a new family of proteins. Armed with this information, investigators working on JAMM proteins involved in various processes can make point mutants to ask whether a protease activity might underlie the process that they are studying. This information in turn could nucleate the identification of substrates and enable the elucidation of a functional pathway. Indeed, we have already shown this for the JAMM protein Rpn11. Rpn11 resides in the proteasome and specifies an isopeptidase activity that cleaves ubiquitin from proteins destined to be degraded by the proteasome. Ablation of the JAMM motif in our Rpn11 blocks this cleavage activity and inactivates the proteasome.