[HTML][HTML] Inactivation of parkin by oxidative stress and C-terminal truncations: a protective role of molecular chaperones
KF Winklhofer, IH Henn, PC Kay-Jackson… - Journal of Biological …, 2003 - ASBMB
Loss of parkin function is linked to autosomal recessive juvenile parkinsonism. Here we
show that proteotoxic stress and short C-terminal truncations induce misfolding of parkin. As
a consequence, wild-type parkin was depleted from a high molecular weight complex and
inactivated by aggregation. Similarly, the pathogenic parkin mutant W453Stop,
characterized by a C-terminal deletion of 13 amino acids, spontaneously adopted a
misfolded conformation. Mutational analysis indicated that C-terminal truncations exceeding …
show that proteotoxic stress and short C-terminal truncations induce misfolding of parkin. As
a consequence, wild-type parkin was depleted from a high molecular weight complex and
inactivated by aggregation. Similarly, the pathogenic parkin mutant W453Stop,
characterized by a C-terminal deletion of 13 amino acids, spontaneously adopted a
misfolded conformation. Mutational analysis indicated that C-terminal truncations exceeding …