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 Ventura

Research output: Chapter in BookChapterResearchpeer-review

Abstract

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. 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.
Original languageEnglish
Title of host publicationMethods in Molecular Biology
Pages237-261
Number of pages24
Volume1958
Edition2nd
ISBN (Electronic)1940-6029
DOIs
Publication statusPublished - 1 Jan 2019

Publication series

NameProtein Supersecondary Structures

Keywords

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

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