Discovering putative prion-like proteins in plasmodium falciparum: a computational and experimental analysis

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  • dc.contributor.author Pallarès, Irantzu
  • dc.contributor.author de Groot, Natalia S.
  • dc.contributor.author Iglesias, Valentin
  • dc.contributor.author Sant'Anna, Ricardo
  • dc.contributor.author Biosca, Arnau
  • dc.contributor.author Fernàndez Busquets, Xavier
  • dc.contributor.author Ventura, Salvador
  • dc.date.accessioned 2019-11-18T08:33:07Z
  • dc.date.available 2019-11-18T08:33:07Z
  • dc.date.issued 2018
  • dc.description.abstract 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.
  • dc.description.sponsorship This work was funded by grants BIO2016-78310-R to SV and BIO2014-52872-R to XF-B (Ministerio de Economía y Competitividad, Spain), which included FEDER funds, and by ICREA, ICREA ACADEMIA 2015 to SV. ISGlobal and IBEC are members of the CERCA Program, Generalitat de Catalunya.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Pallarès I, de Groot NS, Iglesias V, Sant'Anna R, Biosca A, Fernàndez-Busquets X et al. Discovering putative prion-like proteins in plasmodium falciparum: a computational and experimental analysis. Front Microbiol. 2018;9:1737. DOI: 10.3389/fmicb.2018.01737
  • dc.identifier.doi http://dx.doi.org/10.3389/fmicb.2018.01737
  • dc.identifier.issn 1664-302X
  • dc.identifier.uri http://hdl.handle.net/10230/42878
  • dc.language.iso eng
  • dc.publisher Frontiers
  • dc.relation.ispartof Frontiers in Microbiology. 2018;9:1737
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2016-78310-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2014-52872-R
  • dc.rights © 2018 Pallarès, de Groot, Iglesias, Sant’Anna, Biosca, Fernàndez-Busquets and Ventura. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Plasmodium
  • dc.subject.keyword Protein aggregation
  • dc.subject.keyword Amyloid
  • dc.subject.keyword Prion
  • dc.subject.keyword Q/N-rich sequences
  • dc.subject.keyword Protein disorder
  • dc.title Discovering putative prion-like proteins in plasmodium falciparum: a computational and experimental analysis
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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