Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/36012
Title: Crystal structure of the Trypanosoma cruzi EIF4E5 translation factor homologue in complex with mRNA cap-4
Authors: Reolon, Lidia Watanabe
Vichier-Guerre, Sophie
Matos, Bruno Moisés de
Dugué, Laurence
Assunção, Tatiana Reichert da Silva
Zanchin, Nilson Ivo Tonin
Pochet, Sylvie
Guimarães, Beatriz Gomes
Affilliation: Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil / Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências - Bioquímica. Curitiba, PR, Brasil.
Institut Pasteur. Unité de Chimie et Biocatalyse. Paris, France.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil / Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências - Bioquímica. Curitiba, PR, Brasil.
Institut Pasteur. Unité de Chimie et Biocatalyse. Paris, France.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Institut Pasteur. Unité de Chimie et Biocatalyse. Paris, France.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil / Universidade Federal do Paraná. Programa de Pós-Graduação em Ciências - Bioquímica. Curitiba, PR, Brasil.
Abstract: Association of the initiation factor eIF4E with the mRNA cap structure is a key step for translation. Trypanosomatids present six eIF4E homologues, showing a low conservation and also differing significantly from the IF4Es of multicellular eukaryotes. On the mRNA side, while in most eukaryotes the mRNA contains cap-0 (7-methyl-GTP), the trypanosomatid mRNA features a cap-4, which is formed by a cap-0, followed by the AACU sequence containing 2'-O-ribose methylations and base methylations on nucleotides 1 and 4. The studies on eIF4E-cap-4 interaction have been hindered by the difficulty to synthesize this rather elaborated cap-4 sequence. To overcome this problem, we applied a liquid-phase oligonucleotide synthesis strategy and describe for the first time the crystal structure of a trypanosomatid eIF4E (T. cruzi EIF4E5) in complex with cap-4. The TcEIF4E5-cap-4 structure allowed a detailed description of the binding mechanism, revealing the interaction mode for the AACU sequence, with the bases packed in a parallel stacking conformation and involved, together with the methyl groups, in hydrophobic contacts with the protein. This binding mechanism evidences a distinct cap interaction mode in comparison with previously described eIF4E structures and may account for the difference of TcEIF4E5-cap-4 dissociation constant in comparison with other eIF4E homologues.
Keywords: Eukaryotic Initiation Factor-4E
RNA Cap-Binding Proteins
Keywords in spanish: Factor 4E Eucariótico de Iniciación
Proteínas de Unión a Caperuzas de ARN
keywords: Trypanosomatina
DeCS: Fator de Iniciação 4E em Eucariotos
Proteínas de Ligação ao Cap de RNA
Issue Date: 2019
Publisher: Oxford University Press
Citation: REOLON, Lídia Watanabe et al. Crystal structure of the Trypanosoma cruzi EIF4E5 translation factor homologue in complex with mRNA cap-4. Nucleic Acids Research, v. 47, n. 11, p. 5973-5987, 2019.
DOI: 10.1093/nar/gkz339
ISSN: 0305-1048
Copyright: open access
Appears in Collections:PR - ICC - Artigos de Periódicos

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