β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• Amyloid fibrils and beta-barrel proteins share a beta-sheet-rich structure.
• Beta-barrel proteins can form higher-order oligomers and aggregates.
• Recent findings show beta-barrel proteins can adopt cross-beta amyloid folds.

Purpose of the Study:

• To summarize data on amyloid-forming beta-barrel proteins.
• To discuss their physicochemical properties and biological functions.
• To explore the mechanisms and consequences of their amyloidogenesis.

Main Methods:

• Literature review and data synthesis.
• Analysis of structural relationships between beta-folds.
• Discussion of in vitro and in vivo studies.

Main Results:

• Various beta-barrel proteins form amyloid fibrils in vitro.
• Functional amyloids formed by beta-barrel proteins exist in vivo.
• These proteins can adopt beta-barrel topology as on-pathway or off-pathway states during fibrillogenesis.

Conclusions:

• Amyloidogenic beta-barrels have diverse, underestimated functions.
• Beta-barrel oligomers are toxic and implicated in amyloid diseases.
• These proteins represent promising therapeutic targets for incurable diseases.