Ontology highlight
ABSTRACT:
SUBMITTER: Boopathy S
PROVIDER: S-EPMC4491777 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Boopathy Sivakumar S Silvas Tania V TV Tischbein Maeve M Jansen Silvia S Shandilya Shivender M SM Zitzewitz Jill A JA Landers John E JE Goode Bruce L BL Schiffer Celia A CA Bosco Daryl A DA
Proceedings of the National Academy of Sciences of the United States of America 20150608 26
Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-funct ...[more]