The stability of myocilin olfactomedin domain variants provides new insight into glaucoma as a protein misfolding disorder.

ABSTRACT: Myocilin variants, localized to the olfactomedin (OLF) domain, are linked to early-onset, inherited forms of open-angle glaucoma. Disease-causing myocilin variants accumulate within trabecular meshwork cells instead of being secreted to the trabecular extracellular matrix of the eye. We hypothesize that, like in other diseases of protein misfolding, aggregation and downstream pathogenesis originate from the compromised thermal stability of mutant myocilins. In an expansion of our pilot study of four mutants, we compare 21 additional purified OLF variants by using a fluorescence stability assay and investigate the secondary structure of the most stable variants by circular dichroism. Variants with lower melting temperatures are correlated with earlier glaucoma diagnoses. The chemical chaper

SUBMITTER: Burns JN 

PROVIDER: S-EPMC3128542 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature