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Formation of Cross-Beta Supersecondary Structure by Soft-Amyloid Cores: Strategies for Their Prediction and Characterization

  • M. Rosario Fernández
  • Irantzu Pallarès
  • Valentín Iglesias
  • Jaime Santos
  • Salvador VenturaEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1958)

Abstract

Proteins with prion-like behavior are attracting an increasing interest, since accumulating evidences indicate that they play relevant roles both in health and disease. The self-assembly of these proteins into insoluble aggregates is associated with severe neuropathological processes such as amyotrophic lateral sclerosis (ALS). However, in normal conditions, they are known to accomplish a wide range of functional roles. The conformational duality of prion-like proteins is often encoded in specific protein regions, named prion-like domains (PrLDs). PrLDs are usually long and disordered regions of low complexity. We have shown that PrLDs might contain soft-amyloid cores that contribute significantly to trigger their aggregation, as well as to support their propagation. Further exploration of the role of these sequences in the conformational conversion of prion-like proteins might provide novel insights into the mechanism of action and regulation of these polypeptides, enabling the future development of therapeutic strategies. Here, we describe a set of methodologies aimed to identify and characterize these short amyloid stretches in a protein or proteome of interest, ranging from in silico detection to in vitro and in vivo evaluation and validation.

Key words

Protein aggregation Amyloid Soft-amyloid core Fibril Cross-beta-sheet Bioinformatics Prion-like 

Notes

Acknowledgments

This work was funded by the Spanish Ministry of Economy and Competitiveness BIO2016-783-78310-R to S.V. and by ICREA, ICREA-Academia 2015 to S.V.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • M. Rosario Fernández
    • 1
    • 2
  • Irantzu Pallarès
    • 1
    • 2
  • Valentín Iglesias
    • 1
    • 2
  • Jaime Santos
    • 1
    • 2
  • Salvador Ventura
    • 1
    • 2
    Email author
  1. 1.Institut de Biotecnologia i de BiomedicinaUniversitat Autònoma de BarcelonaBarcelonaSpain
  2. 2.Departament de Bioquímica i Biologia MolecularUniversitat Autònoma de BarcelonaBarcelonaSpain

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