Amino acid sequence determinants and molecular chaperones in amyloid fibril formation

• Published in: Biochemical and biophysical research communications Vol. 396; no. 1; pp. 2 - 6
• Main Authors: Nerelius, Charlotte, Fitzen, Michael, Johansson, Jan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.05.2010
• Subjects: Alzheimer’s disease; Amino Acid Sequence; Amyloid - chemistry; Amyloid - metabolism; Amyloidosis - metabolism; Biochemistry and Molecular Biology; Biofysik; Biokemi och molekylärbiologi; Biophysics; Brichos; Humans; Medicin och hälsovetenskap; Molecular Chaperones - metabolism; Neurodegenerative Diseases - metabolism; Prion; Protein Folding; Protein misfolding; Pulmonary Surfactant-Associated Protein C - chemistry; Pulmonary Surfactant-Associated Protein C - metabolism; Secondary structure; Surfactant protein C; Surfactant protein C; RDS; Aβ; Protein misfolding; Alzheimer’s disease; Hsp; SP-C; Prion; Brichos; Secondary structure
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2010.02.105

Amyloid consists of cross-β-sheet fibrils and is associated with about 25 human diseases, including several neurodegenerative diseases, systemic and localized amyloidoses and type II diabetes mellitus. Amyloid-forming proteins differ in structures and sequences, and it is to a large extent unknown what makes them convert from their native conformations into amyloid. In this review, current understanding of amino acid sequence determinants and the effects of molecular chaperones on amyloid formation are discussed. Studies of the nonpolar, transmembrane surfactant protein C (SP-C) have revealed amino acid sequence features that determine its amyloid fibril formation, features that are also found in the amyloid β-peptide in Alzheimer’s disease and the prion protein. Moreover, a proprotein chaperone domain (CTC Brichos) that prevents amyloid-like aggregation during proSP-C biosynthesis can prevent fibril formation also of other amyloidogenic proteins.