Evidence for S₃₃₁-G-S-L within the amyloid core of myocilin olfactomedin domain fibrils based on low-resolution 3D solid-state NMR spectra.

ABSTRACT: Myocilin-associated glaucoma is a protein-conformational disorder associated with formation of a toxic amyloid-like aggregate. Numerous destabilizing single point variants, distributed across the myocilin olfactomedin β-propeller (OLF, myocilin residues 245-504, 30 kDa) are associated with accelerated disease progression. In vitro, wild type (WT) OLF can be promoted to form thioflavin T (ThT)-positive fibrils under mildly destabilizing (37°C, pH 7.2) conditions. Consistent with the notion that only a small number of residues within a protein are responsible for amyloid formation, 3D ¹³C-¹³C solid-state NMR spectra show that OLF fibrils are likely to be composed of only about one third of the overall sequence. Here, we probe the residue composition of fibrils fo

SUBMITTER: Saccuzzo EG 

PROVIDER: S-EPMC11326258 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature