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| Content Provider | Directory of Open Access Journals (DOAJ) |
|---|---|
| Author | Melanie Y. Pullen Conrad C. Weihl Heather L. True |
| Abstract | The misfolding and aggregation of proteins is often implicated in the development and progression of degenerative diseases. Heat shock proteins (HSPs), such as the ubiquitously expressed Type II Hsp40 molecular chaperone, DNAJB6, assist in protein folding and disaggregation. Historically, mutations within the DNAJB6 G/F domain have been associated with Limb-Girdle Muscular Dystrophy type 1D, now referred to as LGMDD1, a dominantly inherited degenerative disease. Recently, novel mutations within the J domain of DNAJB6 have been reported in patients with LGMDD1. Since novel myopathy-causing mutations in the Hsp40 J domain have yet to be characterized and both the function of DNAJB6 in skeletal muscle and the clients of this chaperone are unknown, we set out to assess the effect of these mutations on chaperone function using the genetically tractable yeast system. The essential yeast Type II Hsp40, Sis1, is homologous to DNAJB6 and is involved in the propagation of yeast prions. Using phenotypic, biochemical, and functional assays we found that homologous mutations in the Sis1 J domain differentially alter the processing of specific yeast prion strains, as well as a non-prion substrate. These data suggest that the newly-identified mutations in the J domain of DNAJB6 cause aberrant chaperone function that leads to the pathogenesis in LGMDD1. |
| e-ISSN | 19326203 |
| DOI | 10.1371/journal.pone.0234207 |
| Journal | PLoS ONE |
| Issue Number | 6 |
| Volume Number | 15 |
| Language | English |
| Publisher | Public Library of Science (PLoS) |
| Publisher Date | 2020-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Medicine Science |
| Content Type | Text |
| Resource Type | Article |
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