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Protein Supersecondary Structures pp 237–261Cite as

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

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Part of the book series: Methods in Molecular Biology ((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.

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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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Authors and Affiliations

  1. Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, Spain

    M. Rosario Fernández, Irantzu Pallarès, Valentín Iglesias, Jaime Santos & Salvador Ventura

  2. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain

    M. Rosario Fernández, Irantzu Pallarès, Valentín Iglesias, Jaime Santos & Salvador Ventura

Authors
  1. M. Rosario Fernández
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  2. Irantzu Pallarès
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  3. Valentín Iglesias
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  4. Jaime Santos
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  5. Salvador Ventura
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Corresponding author

Correspondence to Salvador Ventura .

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Editors and Affiliations

  1. Department of Mathematics, Rutgers University, Piscataway, NJ, USA

    Alexander E. Kister

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Fernández, M.R., Pallarès, I., Iglesias, V., Santos, J., Ventura, S. (2019). Formation of Cross-Beta Supersecondary Structure by Soft-Amyloid Cores: Strategies for Their Prediction and Characterization. In: Kister, A. (eds) Protein Supersecondary Structures. Methods in Molecular Biology, vol 1958. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9161-7_12

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  • DOI: https://doi.org/10.1007/978-1-4939-9161-7_12

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