Acknowledgments

This work was supported by the NIH NINDS (NS39112), the ALS Association, and the Robert A. Welch Foundation (AQ-1399). LJW was supported in part by a predoctoral fellowship from the American Federation for Aging Research and in part by a Ford Foundation Predoctoral Fellowship for Minorities. Collaborative efforts on the Zn-H46R structure by R. Strange, M. Hough, S. Antonyuk, and S. Hasnain (CLRC Lab, Daresbury, UK) and on 20 S proteasome digestion studies by R. Levine and L. Di Noto (NIH) are gratefully acknowledged. We thank Alex Taylor and Stephen Holloway for help with the figures, and members of the J. S. Valentine lab for helpful discussions.

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