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Adv Exp Med Biol. 2017;989:93-107. doi: 10.1007/978-3-319-57348-9_8.

Exploring Amyloidogenicity of Clusterin: A Structural and Bioinformatics Analysis.

Author information

1
Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, 15701, Greece.
2
Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, 15701, Greece. veconom@biol.uoa.gr.

Abstract

Clusterin, a multitasking glycoprotein, is a protein highly conserved amongst mammals. In humans, Clusterin is mainly a secreted protein, described as an extracellular chaperone with the capability of interacting with a broad spectrum of molecules. In neurodegenerative diseases, such as Alzheimer's disease, it is an amyloid associated protein, co-localized with fibrillar deposits in amyloid plaques in systemic or localized amyloidoses. An 'aggregation-prone' segment (NFHAMFQ) was located within the Clusterin α-chain sequence using AMYLPRED, a consensus method for the prediction of amyloid propensity, developed in our lab. This peptide was synthesized and was found to self-assemble into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal. All experimental results verify that this human Clusterin peptide-analogue, possesses high aggregation potency. Additional computational analysis highlighted novel and at the same time, unexplored features of human Clusterin.

KEYWORDS:

Aggregation-prediction algorithm; Alzheimer’s disease; Clusterin; Consensus algorithm; Neurodegenerative disease; Protein network; “Aggregation-prone” peptides

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