Structural models of amyloid-like fibrils

Area of Science:

• Biochemistry
• Structural Biology
• Biophysics

Background:

• Amyloid fibrils are insoluble protein aggregates implicated in various diseases.
• Amyloid-like fibrils can be formed in vitro from soluble proteins.
• Despite diverse origins, these fibrils share common structural properties.

Purpose of the Study:

• To review and categorize proposed structural models for amyloid and amyloid-like fibrils.
• To relate features of these models to common fibril properties.
• To assess the explanatory power of different model classes.

Main Methods:

• Literature review of structural models for amyloid and amyloid-like fibrils.
• Classification of models into three categories: Refolding, Gain-of-Interaction, and Natively Disordered.
• Analysis of how each model class explains common fibril properties.

Main Results:

• Refolding models: propose distinct native and fibrillar states, driven by backbone interactions.
• Gain-of-Interaction models: suggest native-like structures, emphasizing specific sequences and cross-beta structures.
• Natively Disordered models: combine aspects of both Refolding and Gain-of-Interaction models.

Conclusions:

• Each model class explains certain amyloid fibril properties.
• Gain-of-Interaction models, particularly those with a cross-beta spine, explain a broader range of properties.
• No single current model completely explains all observed amyloid fibril behaviors.