Structural analysis of the DAP5 MIF4G domain and its interaction with eIF4A.
Structure
; 21(4): 517-27, 2013 Apr 02.
Article
em En
| MEDLINE
| ID: mdl-23478064
ABSTRACT
Death-associated protein 5 (DAP5/p97) is a homolog of the eukaryotic initiation factor 4G (eIF4G) that promotes the IRES-driven translation of multiple cellular mRNAs. Central to its function is the middle domain (MIF4G), which recruits the RNA helicase eIF4A. The middle domain of eIF4G consists of tandem HEAT repeats that coalesce to form a solenoid-type structure. Here, we report the crystal structure of the DAP5 MIF4G domain. Its overall fold is very similar to that of eIF4G; however, significant conformational variations impart distinct surface properties that could explain the observed differences in IRES binding between the two proteins. Interestingly, quantitative analysis of the DAP5-eIF4A interaction using isothermal titration calorimetry reveals a 10-fold lower affinity than with the eIF4G-eIF4A interaction that appears to affect their ability to stimulate eIF4A RNA unwinding activity in vitro. This difference in stability of the complex may have functional implications in selecting the mode of translation initiation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
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Biossíntese de Proteínas
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Modelos Moleculares
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Fator de Iniciação 4A em Eucariotos
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Fator de Iniciação Eucariótico 4G
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article