Structural and Functional Insights into Human Re-initiation Complexes.
Mol Cell
; 67(3): 447-456.e7, 2017 Aug 03.
Article
em En
| MEDLINE
| ID: mdl-28732596
ABSTRACT
After having translated short upstream open reading frames, ribosomes can re-initiate translation on the same mRNA. This process, referred to as re-initiation, controls the translation of a large fraction of mammalian cellular mRNAs, many of which are important in cancer. Key ribosomal binding proteins involved in re-initiation are the eukaryotic translation initiation factor 2D (eIF2D) or the homologous complex of MCT-1/DENR. We determined the structures of these factors bound to the human 40S ribosomal subunit in complex with initiator tRNA positioned on an mRNA start codon in the P-site using a combination of cryoelectron microscopy and X-ray crystallography. The structures, supported by biochemical experiments, reveal how eIF2D emulates the function of several canonical translation initiation factors by using three independent, flexibly connected RNA binding domains to simultaneously monitor codon-anticodon interactions in the ribosomal P-site and position the initiator tRNA.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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RNA de Transferência
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Fator de Iniciação 2 em Eucariotos
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Proteínas Oncogênicas
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Proteínas de Ciclo Celular
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Sítio de Iniciação de Transcrição
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Fatores de Iniciação em Eucariotos
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Subunidades Ribossômicas Menores de Eucariotos
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Iniciação da Transcrição Genética
Limite:
Humans
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Suíça