Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association
The amyloid conformation is considered a fundamental state of proteins and the propensity to populate it a generic property of polypeptides. Multiple proteome-wide analyses addressed the presence of amyloidogenic regions in proteins, nurturing our understanding of their nature and biological implica...
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doaj-1b52041efa614ed795d10b029b3ec0502021-08-04T04:19:28ZengElsevierComputational and Structural Biotechnology Journal2001-03702021-01-011941924206Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease associationJaime Santos0Irantzu Pallarès1Valentín Iglesias2Salvador Ventura3Corresponding authors at: Institut de Biotecnologia i de Biomedicina, Parc de Recerca UAB, Mòdul B, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain.; Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, SpainCorresponding authors at: Institut de Biotecnologia i de Biomedicina, Parc de Recerca UAB, Mòdul B, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain.; Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, SpainThe amyloid conformation is considered a fundamental state of proteins and the propensity to populate it a generic property of polypeptides. Multiple proteome-wide analyses addressed the presence of amyloidogenic regions in proteins, nurturing our understanding of their nature and biological implications. However, these analyses focused on highly aggregation-prone and hydrophobic stretches that are only marginally found in intrinsically disordered regions (IDRs). Here, we explore the prevalence of cryptic amyloidogenic regions (CARs) of polar nature in IDRs. CARs are widespread in IDRs and associated with IDPs function, with particular involvement in protein–protein interactions, but their presence is also connected to a risk of malfunction. By exploring this function/malfunction dichotomy, we speculate that ancestral CARs might have evolved into functional interacting regions playing a significant role in protein evolution at the origins of life.http://www.sciencedirect.com/science/article/pii/S2001037021003093AmyloidAggregationProtein disorderIntrinsically disordered proteinsProtein–protein interactionsEvolution |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jaime Santos Irantzu Pallarès Valentín Iglesias Salvador Ventura |
spellingShingle |
Jaime Santos Irantzu Pallarès Valentín Iglesias Salvador Ventura Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association Computational and Structural Biotechnology Journal Amyloid Aggregation Protein disorder Intrinsically disordered proteins Protein–protein interactions Evolution |
author_facet |
Jaime Santos Irantzu Pallarès Valentín Iglesias Salvador Ventura |
author_sort |
Jaime Santos |
title |
Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association |
title_short |
Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association |
title_full |
Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association |
title_fullStr |
Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association |
title_full_unstemmed |
Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association |
title_sort |
cryptic amyloidogenic regions in intrinsically disordered proteins: function and disease association |
publisher |
Elsevier |
series |
Computational and Structural Biotechnology Journal |
issn |
2001-0370 |
publishDate |
2021-01-01 |
description |
The amyloid conformation is considered a fundamental state of proteins and the propensity to populate it a generic property of polypeptides. Multiple proteome-wide analyses addressed the presence of amyloidogenic regions in proteins, nurturing our understanding of their nature and biological implications. However, these analyses focused on highly aggregation-prone and hydrophobic stretches that are only marginally found in intrinsically disordered regions (IDRs). Here, we explore the prevalence of cryptic amyloidogenic regions (CARs) of polar nature in IDRs. CARs are widespread in IDRs and associated with IDPs function, with particular involvement in protein–protein interactions, but their presence is also connected to a risk of malfunction. By exploring this function/malfunction dichotomy, we speculate that ancestral CARs might have evolved into functional interacting regions playing a significant role in protein evolution at the origins of life. |
topic |
Amyloid Aggregation Protein disorder Intrinsically disordered proteins Protein–protein interactions Evolution |
url |
http://www.sciencedirect.com/science/article/pii/S2001037021003093 |
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