Exploring Amyloidogenicity of Clusterin: A Structural and Bioinformatics Analysis

Area of Science:

• Biochemistry
• Neuroscience
• Structural Biology

Background:

• Clusterin is a conserved, secreted glycoprotein acting as an extracellular chaperone.
• In neurodegenerative diseases like Alzheimer's, Clusterin is associated with amyloid plaques.
• Amyloid formation is a key pathological hallmark in various systemic and localized amyloidoses.

Purpose of the Study:

• To identify and characterize aggregation-prone regions within human Clusterin.
• To investigate the in vitro self-assembly properties of a specific Clusterin peptide segment.
• To explore novel features of human Clusterin relevant to amyloid formation.

Main Methods:

• In silico prediction of amyloid propensity using the AMYLPRED tool.
• Synthesis of the identified 'aggregation-prone' peptide segment (NFHAMFQ).
• In vitro biophysical characterization: electron microscopy, X-ray fiber diffraction, ATR-FTIR, and Congo red staining.

Main Results:

• A specific 'aggregation-prone' segment (NFHAMFQ) was identified in the Clusterin α-chain.
• The synthesized peptide self-assembled into amyloid-like fibrils in vitro.
• Experimental data confirmed the high aggregation potency of this human Clusterin peptide analogue.

Conclusions:

• The identified peptide segment from human Clusterin exhibits significant amyloidogenic potential.
• This study validates the aggregation propensity of a specific Clusterin sequence.
• Findings offer novel insights into the unexplored structural and functional aspects of Clusterin in amyloid-related processes.