Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental Analysis
Prions are a singular subset of proteins able to switch between a soluble conformation and a self-perpetuating amyloid state. Traditionally associated with neurodegenerative diseases, increasing evidence indicates that organisms exploit prion-like mechanisms for beneficial purposes. The ability to t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01737/full |
| _version_ | 1811304243647217664 |
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| author | Irantzu Pallarès Irantzu Pallarès Natalia S. de Groot Natalia S. de Groot Valentín Iglesias Valentín Iglesias Ricardo Sant’Anna Ricardo Sant’Anna Arnau Biosca Arnau Biosca Arnau Biosca Xavier Fernàndez-Busquets Xavier Fernàndez-Busquets Xavier Fernàndez-Busquets Salvador Ventura Salvador Ventura |
| author_facet | Irantzu Pallarès Irantzu Pallarès Natalia S. de Groot Natalia S. de Groot Valentín Iglesias Valentín Iglesias Ricardo Sant’Anna Ricardo Sant’Anna Arnau Biosca Arnau Biosca Arnau Biosca Xavier Fernàndez-Busquets Xavier Fernàndez-Busquets Xavier Fernàndez-Busquets Salvador Ventura Salvador Ventura |
| author_sort | Irantzu Pallarès |
| collection | DOAJ |
| description | Prions are a singular subset of proteins able to switch between a soluble conformation and a self-perpetuating amyloid state. Traditionally associated with neurodegenerative diseases, increasing evidence indicates that organisms exploit prion-like mechanisms for beneficial purposes. The ability to transit between conformations is encoded in the so-called prion domains, long disordered regions usually enriched in glutamine/asparagine residues. Interestingly, Plasmodium falciparum, the parasite that causes the most virulent form of malaria, is exceptionally rich in proteins bearing long Q/N-rich sequence stretches, accounting for roughly 30% of the proteome. This biased composition suggests that these protein regions might correspond to prion-like domains (PrLDs) and potentially form amyloid assemblies. To investigate this possibility, we performed a stringent computational survey for Q/N-rich PrLDs on P. falciparum. Our data indicate that ∼10% of P. falciparum protein sequences have prionic signatures, and that this subproteome is enriched in regulatory proteins, such as transcription factors and RNA-binding proteins. Furthermore, we experimentally demonstrate for several of the identified PrLDs that, despite their disordered nature, they contain inner short sequences able to spontaneously self-assemble into amyloid-like structures. Although the ability of these sequences to nucleate the conformational conversion of the respective full-length proteins should still be demonstrated, our analysis suggests that, as previously described for other organisms, prion-like proteins might also play a functional role in P. falciparum. |
| first_indexed | 2024-04-13T08:03:33Z |
| format | Article |
| id | doaj.art-71ed10977cab4c68a067de671aeeaa7e |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T08:03:33Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-71ed10977cab4c68a067de671aeeaa7e2022-12-22T02:55:14ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-08-01910.3389/fmicb.2018.01737381158Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental AnalysisIrantzu Pallarès0Irantzu Pallarès1Natalia S. de Groot2Natalia S. de Groot3Valentín Iglesias4Valentín Iglesias5Ricardo Sant’Anna6Ricardo Sant’Anna7Arnau Biosca8Arnau Biosca9Arnau Biosca10Xavier Fernàndez-Busquets11Xavier Fernàndez-Busquets12Xavier Fernàndez-Busquets13Salvador Ventura14Salvador Ventura15Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, SpainDepartament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainCentre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, SpainUniversitat Pompeu Fabra, Barcelona, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, SpainDepartament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, SpainDepartament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainNanomalaria Group, Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, SpainBarcelona Institute for Global Health, Barcelona Centre for International Health Research (Hospital Clínic – Universitat de Barcelona), Barcelona, SpainInstitute of Nanoscience and Nanotechnology, University of Barcelona, Barcelona, SpainNanomalaria Group, Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, SpainBarcelona Institute for Global Health, Barcelona Centre for International Health Research (Hospital Clínic – Universitat de Barcelona), Barcelona, SpainInstitute of Nanoscience and Nanotechnology, University of Barcelona, Barcelona, SpainInstitut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, SpainDepartament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainPrions are a singular subset of proteins able to switch between a soluble conformation and a self-perpetuating amyloid state. Traditionally associated with neurodegenerative diseases, increasing evidence indicates that organisms exploit prion-like mechanisms for beneficial purposes. The ability to transit between conformations is encoded in the so-called prion domains, long disordered regions usually enriched in glutamine/asparagine residues. Interestingly, Plasmodium falciparum, the parasite that causes the most virulent form of malaria, is exceptionally rich in proteins bearing long Q/N-rich sequence stretches, accounting for roughly 30% of the proteome. This biased composition suggests that these protein regions might correspond to prion-like domains (PrLDs) and potentially form amyloid assemblies. To investigate this possibility, we performed a stringent computational survey for Q/N-rich PrLDs on P. falciparum. Our data indicate that ∼10% of P. falciparum protein sequences have prionic signatures, and that this subproteome is enriched in regulatory proteins, such as transcription factors and RNA-binding proteins. Furthermore, we experimentally demonstrate for several of the identified PrLDs that, despite their disordered nature, they contain inner short sequences able to spontaneously self-assemble into amyloid-like structures. Although the ability of these sequences to nucleate the conformational conversion of the respective full-length proteins should still be demonstrated, our analysis suggests that, as previously described for other organisms, prion-like proteins might also play a functional role in P. falciparum.https://www.frontiersin.org/article/10.3389/fmicb.2018.01737/fullPlasmodiumprotein aggregationamyloidprionQ/N-rich sequencesprotein disorder |
| spellingShingle | Irantzu Pallarès Irantzu Pallarès Natalia S. de Groot Natalia S. de Groot Valentín Iglesias Valentín Iglesias Ricardo Sant’Anna Ricardo Sant’Anna Arnau Biosca Arnau Biosca Arnau Biosca Xavier Fernàndez-Busquets Xavier Fernàndez-Busquets Xavier Fernàndez-Busquets Salvador Ventura Salvador Ventura Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental Analysis Frontiers in Microbiology Plasmodium protein aggregation amyloid prion Q/N-rich sequences protein disorder |
| title | Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental Analysis |
| title_full | Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental Analysis |
| title_fullStr | Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental Analysis |
| title_full_unstemmed | Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental Analysis |
| title_short | Discovering Putative Prion-Like Proteins in Plasmodium falciparum: A Computational and Experimental Analysis |
| title_sort | discovering putative prion like proteins in plasmodium falciparum a computational and experimental analysis |
| topic | Plasmodium protein aggregation amyloid prion Q/N-rich sequences protein disorder |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.01737/full |
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