Disparate Mutations Confer Therapeutic Gain of Hsp104 Function.

@article{Jackrel2015DisparateMC,
  title={Disparate Mutations Confer Therapeutic Gain of Hsp104 Function.},
  author={Meredith E. Jackrel and Keolamau Yee and Amber Tariq and Annie I. Chen and James Shorter},
  journal={ACS chemical biology},
  year={2015},
  volume={10 12},
  pages={
          2672-9
        }
}
Hsp104, a protein disaggregase from yeast, can be engineered and potentiated to counter TDP-43, FUS, or α-synuclein misfolding and toxicity implicated in neurodegenerative disease. Here, we reveal that extraordinarily disparate mutations potentiate Hsp104. Remarkably, diverse single missense mutations at 20 different positions interspersed throughout the middle domain (MD) and small domain of nucleotide-binding domain 1 (NBD1) confer a therapeutic gain of Hsp104 function. Moreover, potentiation… Expand
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