Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy

Detalhes bibliográficos
Autor(a) principal: Biembengut, Ísis Venturi
Data de Publicação: 2022
Outros Autores: Shigunov, Patrícia, Frota, Natalia F., Lourenzoni, Marcos R., Souza, Tatiana de Arruda Campos Brasil de
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/55233
Resumo: Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.
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spelling Biembengut, Ísis VenturiShigunov, PatríciaFrota, Natalia F.Lourenzoni, Marcos R.Souza, Tatiana de Arruda Campos Brasil de2022-10-21T16:01:05Z2022-10-21T16:01:05Z2022BIEMBENGUT, Ísis V. et al. Molecular dynamics of CYFIP2 protein and its R87C variant related to early infantile epileptic encephalopathy. Int. J. Mol. Sci., v. 23, n. 8708, p. 1–16, 2022.1422-0067https://www.arca.fiocruz.br/handle/icict/5523310.3390/ijms23158708porMDPIComplexo Regulador WAVEBrain DiseasesEpilepsyMolecular DynamicsEncefalopatíasEpilepsiaEncéphalopathiesÉpilepsieEncefalopatiasEpilepsiaDinâmica MolecularMolecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.Universidade Federal do Ceará. Fortaleza, CE, Brasil. / Fundação Oswaldo Cruz Ceará. Grupo de Pesquisa em Engenharia de Proteínas e Soluções em Saúde. Eusébio, CE, Brasil.Fundação Oswaldo Cruz Ceará. Grupo de Pesquisa em Engenharia de Proteínas e Soluções em Saúde. Eusébio, CE, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.The CYFIP2 protein (cytoplasmic FMR1-interacting protein 2) is part of the WAVE regulatory complex (WRC). CYFIP2 was recently correlated to neurological disorders by the association of the R87C variant with early infantile epileptic encephalopathy (EIEE) patients. In this set of syndromes, the epileptic spasms and seizures since early childhood lead to impaired neurological development in children. Inside the WRC, the variant residue is at the CYFIP2 andWAVE1 protein interface. Thus, the hypothesis is that the R87C modification weakens this interaction, allowing the WRC complex’s constant activation. This work aimed to investigate the impacts of the mutation on the structure of the WRC complex through molecular dynamics simulation. For that, we constructed WRC models containing WAVE1-NCKAP1 proteins complexed with WT or R87C CYFIP2. Our simulations showed a flexibilization of the loop comprising residues 80–110 due to the loss of contacts between internal residues in the R87C CYFIP2 as well as the key role of residues R/C87, E624, and E689 in structural modification. These data could explain the mechanism by which the mutation impairs the stability and proper regulation of the WRC.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALijms-23-08708ok.pdfijms-23-08708ok.pdfapplication/pdf5403161https://www.arca.fiocruz.br/bitstream/icict/55233/2/ijms-23-08708ok.pdfd917ef91644d0461284a5ccc9421cc34MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/55233/1/license.txt5a560609d32a3863062d77ff32785d58MD51icict/552332022-10-21 13:01:06.227oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-10-21T16:01:06Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy
title Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy
spellingShingle Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy
Biembengut, Ísis Venturi
Complexo Regulador WAVE
Brain Diseases
Epilepsy
Molecular Dynamics
Encefalopatías
Epilepsia
Encéphalopathies
Épilepsie
Encefalopatias
Epilepsia
Dinâmica Molecular
title_short Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy
title_full Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy
title_fullStr Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy
title_full_unstemmed Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy
title_sort Molecular dynamics of CYFIP2 protein and Its R87C variant related to early infantile epileptic encephalopathy
author Biembengut, Ísis Venturi
author_facet Biembengut, Ísis Venturi
Shigunov, Patrícia
Frota, Natalia F.
Lourenzoni, Marcos R.
Souza, Tatiana de Arruda Campos Brasil de
author_role author
author2 Shigunov, Patrícia
Frota, Natalia F.
Lourenzoni, Marcos R.
Souza, Tatiana de Arruda Campos Brasil de
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Biembengut, Ísis Venturi
Shigunov, Patrícia
Frota, Natalia F.
Lourenzoni, Marcos R.
Souza, Tatiana de Arruda Campos Brasil de
dc.subject.other.en_US.fl_str_mv Complexo Regulador WAVE
topic Complexo Regulador WAVE
Brain Diseases
Epilepsy
Molecular Dynamics
Encefalopatías
Epilepsia
Encéphalopathies
Épilepsie
Encefalopatias
Epilepsia
Dinâmica Molecular
dc.subject.en.en_US.fl_str_mv Brain Diseases
Epilepsy
Molecular Dynamics
dc.subject.es.en_US.fl_str_mv Encefalopatías
Epilepsia
dc.subject.fr.en_US.fl_str_mv Encéphalopathies
Épilepsie
dc.subject.decs.en_US.fl_str_mv Encefalopatias
Epilepsia
Dinâmica Molecular
description Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-10-21T16:01:05Z
dc.date.available.fl_str_mv 2022-10-21T16:01:05Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv BIEMBENGUT, Ísis V. et al. Molecular dynamics of CYFIP2 protein and its R87C variant related to early infantile epileptic encephalopathy. Int. J. Mol. Sci., v. 23, n. 8708, p. 1–16, 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/55233
dc.identifier.issn.en_US.fl_str_mv 1422-0067
dc.identifier.doi.none.fl_str_mv 10.3390/ijms23158708
identifier_str_mv BIEMBENGUT, Ísis V. et al. Molecular dynamics of CYFIP2 protein and its R87C variant related to early infantile epileptic encephalopathy. Int. J. Mol. Sci., v. 23, n. 8708, p. 1–16, 2022.
1422-0067
10.3390/ijms23158708
url https://www.arca.fiocruz.br/handle/icict/55233
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/55233/2/ijms-23-08708ok.pdf
https://www.arca.fiocruz.br/bitstream/icict/55233/1/license.txt
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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