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eIF4G stimulates the activity of the DEAD box protein eIF4A by a conformational guidance mechanism

Hilbert, M.. (2011) eIF4G stimulates the activity of the DEAD box protein eIF4A by a conformational guidance mechanism. Nucleic Acids Research, 39 (6). pp. 2260-2270.

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Official URL: http://edoc.unibas.ch/dok/A5842429

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Abstract

The activity of eIF4A, a key player in translation initiation, is regulated by other translation factors through currently unknown mechanisms. Here, we provide the necessary framework to understand the mechanism of eIF4A?s regulation by eIF4G. In solution, eIF4A adopts a defined conformation that is different from the crystal structure. Binding of eIF4G induces a ?half-open? conformation by interactions with both domains, such that the helicase motifs are pre-aligned for activation. A primary interface acts as an anchor for complex formation. We show here that formation of the secondary interface is essential for imposing the ?half-open? conformation on eIF4A, and it is critical for the functional interaction of eIF4G with eIF4A. Via this bipartite interaction, eIF4G guides the transition of eIF4A between the ?half-open? and closed conformations, and stimulates its activity by accelerating the rate-limiting step of phosphate release. Subtle changes induced by eIF4G may be amplified by input signals from other translation factors, leading to an efficient regulation of translation initiation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Klostermeier)
UniBasel Contributors:Klostermeier, Dagmar
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0305-1048
e-ISSN:1362-4962
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:10 Oct 2017 08:43
Deposited On:08 Jun 2012 06:51

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