Kinetic control in protein folding for light chain amyloidosis and the differential effects of somatic mutations.

ABSTRACT: Light chain amyloidosis is a devastating disease where immunoglobulin light chains form amyloid fibrils, resulting in organ dysfunction and death. Previous studies have shown a direct correlation between the protein thermodynamic stability and the propensity for amyloid formation for some proteins involved in light chain amyloidosis. Here we investigate the effect of somatic mutations on protein stability and in vitro fibril formation of single and double restorative mutants of the protein AL-103 compared to the wild-type germline control protein. A scan rate dependence and hysteresis in the thermal unfolding and refolding was observed for all proteins. This indicates that the unfolding/refolding reaction is kinetically determined with different kinetic constants for unfolding and refoldin

SUBMITTER: Blancas-Mejia LM 

PROVIDER: S-EPMC3892967 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature