Insights into the mechanism of cystatin C oligomer and amyloid formation and its interaction with β-amyloid.

ABSTRACT: Cystatin C (CysC) is a versatile and ubiquitously-expressed member of the cysteine protease inhibitor family that is present at notably high concentrations in cerebrospinal fluid. Under mildly denaturing conditions, CysC forms inactive domain-swapped dimers. A destabilizing mutation, L68Q, increases the rate of domain-swapping and causes a fatal amyloid disease, hereditary cystatin C amyloid angiopathy. Wild-type (wt) CysC will also aggregate into amyloid fibrils under some conditions. Propagated domain-swapping has been proposed as the mechanism by which CysC fibrils grow. We present evidence that a CysC mutant, V57N, stabilized against domain-swapping, readily forms fibrils, contradicting the propagated domain-swapping hypothesis. Furthermore, in physiological buffer, wt CysC can form ol

SUBMITTER: Perlenfein TJ 

PROVIDER: S-EPMC5500812 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature