Elongation Factor Tu Switch I Element is a Gate for Aminoacyl-tRNA Selection.
J Mol Biol
; 432(9): 3064-3077, 2020 04 17.
Article
en En
| MEDLINE
| ID: mdl-32061931
ABSTRACT
Selection of correct aminoacyl (aa)-tRNA at the ribosomal A site is fundamental to maintaining translational fidelity. Aa-tRNA selection is a multistep process facilitated by the guanosine triphosphatase elongation factor (EF)-Tu. EF-Tu delivers aa-tRNA to the ribosomal A site and participates in tRNA selection. The structural mechanism of how EF-Tu is involved in proofreading remains to be fully resolved. Here, we provide evidence that switch I of EF-Tu facilitates EF-Tu's involvement during aa-tRNA selection. Using structure-based and explicit solvent molecular dynamics simulations based on recent cryo-electron microscopy reconstructions, we studied the conformational change of EF-Tu from the guanosine triphosphate to guanine diphosphate conformation during aa-tRNA accommodation. Switch I of EF-Tu rapidly converts from an α-helix into a ß-hairpin and moves to interact with the acceptor stem of the aa-tRNA. In doing so, switch I gates the movement of the aa-tRNA during accommodation through steric interactions with the acceptor stem. Pharmacological inhibition of the aa-tRNA accommodation pathway prevents the proper positioning of switch I with the aa-tRNA acceptor stem, suggesting that the observed interactions are specific for cognate aa-tRNA substrates, and thus capable of contributing to the fidelity mechanism.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aminoacil-ARN de Transferencia
/
Factor Tu de Elongación Peptídica
/
Proteínas Mitocondriales
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Mol Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos