Exploring Amyloidogenicity of Clusterin: A Structural and Bioinformatics Analysis

  • Paraskevi L. Tsiolaki
  • Katerina C. Nastou
  • Nikolaos N. Louros
  • Stavros J. Hamodrakas
  • Vassiliki A. Iconomidou
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 989)

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

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

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Paraskevi L. Tsiolaki
    • 1
  • Katerina C. Nastou
    • 1
  • Nikolaos N. Louros
    • 1
  • Stavros J. Hamodrakas
    • 1
  • Vassiliki A. Iconomidou
    • 1
  1. 1.Section of Cell Biology and Biophysics, Department of BiologyNational and Kapodistrian University of AthensAthensGreece

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