BIGH3 (TGFBI) Arg124 mutations influence the amyloid conversion of related peptides in vitro.

摘要: Amyloid deposits with Arg124 mutated TGFBI protein have been identified in autosomal dominant blinding corneal dystrophies. We assessed vitro the mechanisms determining amyloid transformation involving mutations of Arg124. Eight peptides synthesized following sequence, centered on codon holding previously reported amyloidogenic and respective controls were studied. Cys124 His124 peptide preparations contained significantly higher amounts than native peptide. Blocking SH group deleting first four NH2-terminal amino acids including Val112-Val113 resulted a decrease fibril formation while deletion nine CONH2-terminal residues increased concentration. Fourrier transformed-infrared spectroscopy analysis different solutions showed an increase β-pleated sheet structures those enhanced yielding. designed (BB1) likely to counteract role formation. Incubation BB1 indeed 35% inhibition formation. Our results are keeping clinical observations mutation-linked amyloidosis show importance Val112–Val113, disulfide hydrogen bonding increasing conformation These findings shed new light molecular amyloidogenesis encourage further research use specifically as putative therapeutic agents for these disabling diseases.