Structural characterization of human Uch37

Uch37 is a de-ubiquitylating enzyme that is functionally linked with the 26S proteasome via Rpn13, and is essential for metazoan development. Here, we report the X-ray crystal structure of full-length human Uch37 at 2.95 A resolution. Uch37's catalytic domain is similar to those of all UCH enzymes characterized to date. The C-terminal extension is elongated, predominantly helical and contains coiled coil interactions. Additionally, we provide an initial characterization of Uch37's oligomeric state and identify a systematic error in previous analyses of Uch37 activity. Taken together, these data provide a strong foundation for further analysis of Uch37's several functions.