Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and α-Synuclein Proteotoxicity

Summary: Hsp104 is an AAA+ protein disaggregase, which can be potentiated via diverse mutations in its autoregulatory middle domain (MD) to mitigate toxic misfolding of TDP-43, FUS, and α-synuclein implicated in fatal neurodegenerative disorders. Problematically, potentiated MD variants can exhibit...

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Bibliographic Details
Main Authors: Amber Tariq, JiaBei Lin, Meredith E. Jackrel, Christina D. Hesketh, Peter J. Carman, Korrie L. Mack, Rachel Weitzman, Craig Gambogi, Oscar A. Hernandez Murillo, Elizabeth A. Sweeny, Esin Gurpinar, Adam L. Yokom, Stephanie N. Gates, Keolamau Yee, Saurabh Sudesh, Jacob Stillman, Alexandra N. Rizo, Daniel R. Southworth, James Shorter
Format: Article
Language:English
Published: Elsevier 2019-08-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719309738