Characterization of Soft Amyloid Cores in Human Prion-Like Proteins

Batlle, Cristina; Groot, Natalia Sánchez de; Iglesias, Valentín; Navarro, Susanna; Ventura, Salvador

doi:10.1038/s41598-017-09714-z

Cited by 26 publications

(28 citation statements)

References 76 publications

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“…Another thing that caught our attention in terms of viral assembly and prionogenic properties is that in eukaryotes, PrDs are known to be implicated in liquid-liquid phase separation (LLPS) [82][83][84][85] . LLPS is known to be an important process in the nucleation and growth of protein crystals and is suggested as the first step for viral capsid growth 86,87 .…”

Section: Discussionmentioning

confidence: 99%

Prion-like Domains in Eukaryotic Viruses

Tetz

2018

Sci Rep

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Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.

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Section: Discussionmentioning

confidence: 99%

Prion-like Domains in Eukaryotic Viruses

Tetz

2018

Sci Rep

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“…Multiple prion prediction algorithms have been applied to specific reference proteomes to identify human PrLDs [8,13,[38][39][40][41]. While these predictions provide important baseline maps of PrLDs in human proteins, they do not account for the considerable diversity in protein sequences across individuals.…”

Section: Sequence Variation In Human Prlds Leads To Wide Ranges In Esmentioning

confidence: 99%

Natural and pathogenic protein sequence variation affecting prion-like domains within and across human proteomes

Cascarina

Ross

2020

BMC Genomics

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Background: Impaired proteostatic regulation of proteins with prion-like domains (PrLDs) is associated with a variety of human diseases including neurodegenerative disorders, myopathies, and certain forms of cancer. For many of these disorders, current models suggest a prion-like molecular mechanism of disease, whereby proteins aggregate and spread to neighboring cells in an infectious manner. The development of prion prediction algorithms has facilitated the large-scale identification of PrLDs among "reference" proteomes for various organisms. However, the degree to which intraspecies protein sequence diversity influences predicted prion propensity has not been systematically examined. Results: Here, we explore protein sequence variation introduced at genetic, post-transcriptional, and posttranslational levels, and its influence on predicted aggregation propensity for human PrLDs. We find that sequence variation is relatively common among PrLDs and in some cases can result in relatively large differences in predicted prion propensity. Sequence variation introduced at the post-transcriptional level (via alternative splicing) also commonly affects predicted aggregation propensity, often by direct inclusion or exclusion of a PrLD. Finally, analysis of a database of sequence variants associated with human disease reveals a number of mutations within PrLDs that are predicted to increase prion propensity. Conclusions: Our analyses expand the list of candidate human PrLDs, quantitatively estimate the effects of sequence variation on the aggregation propensity of PrLDs, and suggest the involvement of prion-like mechanisms in additional human diseases.

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“…Multiple prion prediction algorithms have been applied to specific reference proteomes to identify human PrLDs (13,(38)(39)(40)(41)(42). While these predictions provide important baseline maps of PrLDs in human proteins, they do not account for the considerable diversity in protein sequences across individuals.…”

Section: Propensitymentioning

confidence: 99%

“…NFAR2 (but not NFAR1) is recruited to stress granules, its recruitment is dependent upon its PrLD, and recruitment of NFAR2 leads to stress granule enlargement (57). A short "amyloid core" from the high-scoring NFAR2 PrLD forms amyloid fibers in vitro (41). ILF3 proteins co-aggregate with mutant p53 (another PrLD-containing protein) in models of ovarian cancer (58).…”

Section: Fig 2 Alternative Splicing Influences Predicted Aggregationmentioning

confidence: 99%

Natural and Pathogenic Protein Sequence Variation Affecting Prion-Like Domains Within and Across Human Proteomes

Cascarina

Ross

2019

Preprint

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Protein aggregation is involved in a variety of muscular and neurodegenerative disorders. For many of these disorders, current models suggest a prion-like molecular mechanism of disease, whereby proteins aggregate and spread to neighboring cells in an infectious manner. A variety of proteins with prion-like domains (PrLDs) have recently been linked to these disorders. The development of prion prediction algorithms has facilitated the large-scale identification of PrLDs among "reference" proteomes for various organisms.However, the degree to which intraspecies protein sequence diversity influences predicted aggregation propensity for PrLDs has not been systematically examined. Here, we explore protein sequence variation introduced at genetic, post-transcriptional, and post-translational levels, and its influence on predicted aggregation propensity for human PrLDs. We find that sequence variation is relatively common among PrLDs and in some cases can result in relatively large differences in predicted aggregation propensity. Analysis of a database of sequence variants associated with human disease reveals a number of mutations within PrLDs that are predicted to increase aggregation propensity. Our analyses expand the list of candidate human PrLDs, estimate the effects of sequence variation on the aggregation propensity of PrLDs, and suggest the involvement of prion-like mechanisms in additional human diseases.

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Characterization of Soft Amyloid Cores in Human Prion-Like Proteins

Cited by 26 publications

References 76 publications

Prion-like Domains in Eukaryotic Viruses

Prion-like Domains in Eukaryotic Viruses

Natural and pathogenic protein sequence variation affecting prion-like domains within and across human proteomes

Natural and Pathogenic Protein Sequence Variation Affecting Prion-Like Domains Within and Across Human Proteomes

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