Hsp104p: a protein disaggregase

Abstract

All newly synthesized proteins must fold to their correct native conformation in order to function. That protein folding in the crowded macromolecular environment of the cell is as efficient as it appears to be is remarkable in itself. However, physical or chemical stresses or the accumulation of aberrant proteins encoded by mutated genes can easily perturb protein folding homeostasis in cells. In the protein biochemistry laboratory the aggregation of proteins can be frustrating and even aggravating, but when partially folded or misfolded proteins aggregate in the cell or even, in the case of systemic amyloidoses or Alzheimer’s Disease, outside the cell, the consequences can be devastating. Molecular chaperones typically play a key role in preventing protein aggregation. However, this monograph describes the biology and biochemistry of yeast Hsp104p, an unconventional molecular chaperone that specializes, not in preventing, but in reversing protein aggregation.