Structures of USP2 and USP14, modeled with ubiquitin and ISG15.

<p>Both USP2 and USP14 accommodate ubiquitin (green) in a shallow groove, measuring approximately 25–30 Å in diameter (view from top shown in the upper panels, view from front shown in the lower panels). Based on these complexes, the C-terminal domain of ISG15 (red) can be modeled into the groove to replace ubiquitin. The N-terminal domain of ISG15 is not involved in the hydrolysis reaction, and is located outside of the catalytic core domain of both proteases. The N-termini of USP2 and USP14 are lacking in these representations and extend to the right side of the structure models.