DNAJB6 mutants display toxic gain of function through unregulated interaction with Hsp70 chaperones.

ABSTRACT: Molecular chaperones are essential cellular components that aid in protein folding and preventing the abnormal aggregation of disease-associated proteins. Mutations in one such chaperone, DNAJB6, were identified in patients with LGMDD1, a dominant autosomal disorder characterized by myofibrillar degeneration and accumulations of aggregated protein within myocytes. The molecular mechanisms through which such mutations cause this dysfunction, however, are not well understood. Here we employ a combination of solution NMR and biochemical assays to investigate the structural and functional changes in LGMDD1 mutants of DNAJB6. Surprisingly, we find that DNAJB6 disease mutants show no reduction in their aggregation-prevention activity in vitro, and instead differ structurally from the WT protein,

SUBMITTER: Abayev-Avraham M 

PROVIDER: S-EPMC10624832 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature