The role of intra and inter-molecular disulfide bonds in modulating amyloidogenesis: A review

• Published in: Archives of biochemistry and biophysics 2022-02, Vol.716, p.109113-109113, Article 109113
• Main Authors: Mitra, Aranyak, Sarkar, Nandini
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - etiology; Amyloidogenic Proteins - chemistry; Amyloidogenic Proteins - metabolism; Amyloidosis; Amyloidosis - etiology; Amyotrophic Lateral Sclerosis - etiology; Conformational flexibility; Diabetes Mellitus, Type 2 - etiology; Disulfide bonds; Disulfides - chemistry; Disulfides - metabolism; Humans; Insulin - chemistry; Intramolecular Lyases - chemistry; Models, Molecular; Molecular interactions; Phosphatidylinositols - metabolism; Prion Diseases - ethnology; Protein Aggregates; Protein Binding; Protein Conformation; Structure-Activity Relationship
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2021.109113

All proteins have the inherent ability to undergo transformation from their native structure to a β sheet rich fibrillar structure, called amyloid when subjected to specific conditions. Proteins with a high propensity to form amyloid fibrils have been implicated in a variety of disorders like Alzheimer's disease, Parkinson's disease, Type II diabetes, Amyotrophic Lateral Sclerosis (ALS) and prion diseases. Among the various critical factors that modulate the process of amyloid formation, disulfide bonds have been identified as one of the key determinants of amyloid propensity in proteins. Studies have shown that intra-molecular disulfide bonds impart stability to the native structure of a protein and decrease the tendency for amyloid aggregation, whereas intermolecular disulfide bonds aid in the process of aggregation. In this review, we will analyze the varying effects of both intra as well as inter-molecular disulfide bonds on the amyloid aggregation propensities of a few proteins associated with amyloid disorders. [Display omitted] •Disulfide bonds affect amyloid aggregation.•Intramolecular disulfide bonds stabilize structure, reduce aggregation.•Intermolecular disulfide bonds enhance interactions, drive amyloidosis.•Intramolecular disulfide bond engineering stabilize protein, can prevent amyloidosis.