Báo cáo Y học: BIGH3 (TGFBI) Arg124 mutations influence the amyloid conversion of related peptides in vitro Implications in the BIGH3-linked corneal dystrophies

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

Authors: Clair-Florent Schmitt-Bernard, Alain Chavanieu, Gudrun Herrada, Guy Subra, Bernard Arnaud, Jacques G. Demaille, Bernard Calas, Ángel Argilés

Field: Biochemistry / Molecular Biology / Ophthalmology

Document Content: This document investigates how mutations at codon Arg124 of the BIGH3 (TGFBI) protein influence the formation of amyloid fibrils in vitro. The study utilizes synthesized peptides corresponding to segments of the TGFBI protein, focusing on the region around codon 124. It examines the impact of specific mutations (Cys124, His124) and structural elements like disulfide bonds, N-terminal sequences (Val112-Val113), and the C-terminal sequence on amyloid fibril formation. The research also explores the potential of a specifically designed peptide (BB1) to inhibit this process. Findings are correlated with clinical observations of hereditary corneal dystrophies linked to BIGH3 mutations, aiming to shed light on the molecular mechanisms of amyloidogenesis and explore therapeutic strategies.

Detailed Table of Contents:

• Amyloid deposits with Arg124 mutated TGFBI protein
• Hereditary corneal dystrophies and the BIGH3 gene
• Experimental Procedures: Synthesis and purification of peptides, Chemicals, Peptide synthesis, In vitro processing of the peptides, Congo red stain, Thioflavine T fluorescence analysis, Electron transmission microscopy, Fourier-Transform Infrared Spectroscopy (FT-IR), Beta-breaker methods
• Results: Role of amino-acid 124, Role of the Cys-Cys disulfide bonds, Role of the NH2-terminal sequence, Role of the CONH2-terminal sequence, Role of hydrogen bonds, Effect of the β-pleated sheet inhibitor on amyloid fibril formation ‘in vitro’
• Discussion
• Acknowledgements
• References