Computational study on the allosteric mechanism of Leishmania major IF4E-1 by 4E-interacting protein-1: Unravelling the determinants of m7GTP cap recognition

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorRice University-
Autor(es): dc.contributorUniversidade Federal do Rio de Janeiro (UFRJ)-
Autor(es): dc.creatorHernández-Alvarez, Lilian-
Autor(es): dc.creatorOliveira Jr, Antonio B-
Autor(es): dc.creatorHernández-González, Jorge Enrique-
Autor(es): dc.creatorChahine, Jorge-
Autor(es): dc.creatorPascutti, Pedro Geraldo-
Autor(es): dc.creatorde Araujo, Alexandre Suman-
Autor(es): dc.creatorde Souza, Fátima Pereira-
Data de aceite: dc.date.accessioned2025-08-21T18:11:43Z-
Data de disponibilização: dc.date.available2025-08-21T18:11:43Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2020-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.csbj.2021.03.036-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/228930-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/228930-
Descrição: dc.descriptionDuring their life cycle, Leishmania parasites display a fine-tuned regulation of the mRNA translation through the differential expression of isoforms of eukaryotic translation initiation factor 4E (LeishIF4Es). The interaction between allosteric modulators such as 4E-interacting proteins (4E-IPs) and LeishIF4E affects the affinity of this initiation factor for the mRNA cap. Here, several computational approaches were employed to elucidate the molecular bases of the previously-reported allosteric modulation in L. major exerted by 4E-IP1 (Lm4E-IP1) on eukaryotic translation initiation factor 4E 1 (LmIF4E-1). Molecular dynamics (MD) simulations and accurate binding free energy calculations (ΔGbind) were combined with network-based modeling of residue-residue correlations. We also describe the differences in internal motions of LmIF4E-1 apo form, cap-bound, and Lm4E-IP1-bound systems. Through community network calculations, the differences in the allosteric pathways of allosterically-inhibited and active forms of LmIF4E-1 were revealed. The ΔGbind values show significant differences between the active and inhibited systems, which are in agreement with the available experimental data. Our study thoroughly describes the dynamical perturbations of LmIF4E-1 cap-binding site triggered by Lm4E-IP1. These findings are not only essential for the understanding of a critical process of trypanosomatids’ gene expression but also for gaining insight into the allostery of eukaryotic IF4Es, which could be useful for structure-based design of drugs against this protein family.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)-
Descrição: dc.descriptionDepartment of Physics Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista Julio de Mesquita Filho São José do Rio Preto-
Descrição: dc.descriptionCenter for Theoretical Biological Physics Rice University-
Descrição: dc.descriptionInstituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de Janeiro-
Descrição: dc.descriptionDepartment of Physics Instituto de Biociências Letras e Ciências Exatas Universidade Estadual Paulista Julio de Mesquita Filho São José do Rio Preto-
Formato: dc.format2027-2044-
Idioma: dc.languageen-
Relação: dc.relationComputational and Structural Biotechnology Journal-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject4E-binding proteins-
Palavras-chave: dc.subjectAdaptive Biasing Force (ABF) calculations-
Palavras-chave: dc.subjectAllostery-
Palavras-chave: dc.subjectEukaryotic Initiation Factor-4E-
Palavras-chave: dc.subjectLeishmania major-
Palavras-chave: dc.subjectMolecular dynamics-
Palavras-chave: dc.subjectmRNA cap-
Título: dc.titleComputational study on the allosteric mechanism of Leishmania major IF4E-1 by 4E-interacting protein-1: Unravelling the determinants of m7GTP cap recognition-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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