Liquid-liquid phase separation and fibrillation of the prion protein modulated by a high-affinity DNA aptamer

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dc.creatorCarolina Oliveira Matos
dc.creatorSotiris Missailidis
dc.creatorJerson Lima da Silva
dc.creatorVladimir N. Uversky
dc.creatorAnderson de Sá Pinheiro
dc.creatorYraima Moura Lopes Cordeiro
dc.creatorYulli Moraes Ferreira Passos
dc.creatorMariana Juliani do Amaral
dc.creatorBruno Macedo da Silva
dc.creatorMatheus Heidemann Tempone
dc.creatorOhanna Cavalcanti de Lima Bezerra
dc.creatorMilton Ozório Moraes
dc.creatorMarcius da Silva Almeida
dc.creatorGerald Weber
dc.date.accessioned2024-02-21T16:52:38Z
dc.date.accessioned2025-09-08T23:07:50Z
dc.date.available2024-02-21T16:52:38Z
dc.date.issued2020
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.description.sponsorshipFAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
dc.identifier.doihttps://doi.org/10.1096/fj.201901897R
dc.identifier.issn1530-6860
dc.identifier.urihttps://hdl.handle.net/1843/64408
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofThe FASEB Journal
dc.rightsAcesso Restrito
dc.subjectÁcido ribonucleico
dc.subjectTransições de fases
dc.subjectPrions
dc.subject.otherNeurodegenerative diseases
dc.subject.otherNucleic acid
dc.subject.otherPhase transitions
dc.subject.otherPrions
dc.subject.otherSELEX
dc.titleLiquid-liquid phase separation and fibrillation of the prion protein modulated by a high-affinity DNA aptamer
dc.typeArtigo de periódico
local.citation.epage385
local.citation.issue1
local.citation.spage365
local.citation.volume34
local.description.resumoStructural conversion of cellular prion protein (PrPC) into scrapie PrP (PrPSc) and subsequent aggregation are key events associated with the onset of transmissible spongiform encephalopathies (TSEs). Experimental evidence supports the role of nucleic acids (NAs) in assisting this conversion. Here, we asked whether PrP undergoes liquid-liquid phase separation (LLPS) and if this process is modulated by NAs. To this end, two 25-mer DNA aptamers, A1 and A2, were selected against the globular domain of recombinant murine PrP (rPrP90-231) using SELEX methodology. Multiparametric structural analysis of these aptamers revealed that A1 adopts a hairpin conformation. Aptamer binding caused partial unfolding of rPrP90-231 and modulated its ability to undergo LLPS and fibrillate. In fact, although free rPrP90-231 phase separated into large droplets, aptamer binding increased the number of droplets but noticeably reduced their size. Strikingly, a modified A1 aptamer that does not adopt a hairpin structure induced formation of amyloid fibrils on the surface of the droplets. We show here that PrP undergoes LLPS, and that the PrP interaction with NAs modulates phase separation and promotes PrP fibrillation in a NA structure and concentration-dependent manner. These results shed new light on the roles of NAs in PrP misfolding and TSEs.
local.identifier.orcidhttps://orcid.org/0000-0003-4890-0510
local.identifier.orcidhttps://orcid.org/0000-0003-1069-0255
local.identifier.orcidhttps://orcid.org/0000-0001-9523-9441
local.identifier.orcidhttps://orcid.org/0000-0002-4037-5857
local.identifier.orcidhttps://orcid.org/0000-0001-5118-6931
local.identifier.orcidhttps://orcid.org/0000-0003-4278-212X
local.identifier.orcidhttps://orcid.org/0000-0003-1247-2606
local.identifier.orcidhttps://orcid.org/0000-0001-9863-3313
local.identifier.orcidhttps://orcid.org/0000-0003-2653-0037
local.identifier.orcidhttps://orcid.org/0000-0003-4921-8185
local.identifier.orcidhttps://orcid.org/0000-0002-2935-1571
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE FÍSICA
local.publisher.initialsUFMG
local.url.externahttps://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.201901897R

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