Effects of maturation on the conformational free-energy landscape of SOD1.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a devastating fatal syndrome characterized by very rapid degeneration of motor neurons. A leading hypothesis is that ALS is caused by toxic protein misfolding and aggregation, as also occurs in many other neurodegenerative disorders, such as prion, Alzheimer's, Parkinson's, and Huntington's diseases. A prominent cause of familial ALS is mutations in the protein superoxide dismutase (SOD1), which promote the formation of misfolded SOD1 conformers that are prone to aberrant interactions both with each other and with other cellular components. We have shown previously that immature SOD1, lacking bound Cu and Zn metal ions and the intrasubunit disulfide bond (apoSOD1^2SH), has a rugged free-energy surface (FES) and exchanges with four other conf

SUBMITTER: Culik RM 

PROVIDER: S-EPMC5856554 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature