PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains

Suzuki, Chikako and Garces, Robert G. and Edmonds, Katherine A. and Hiller, Sebastian and Hyberts, Sven G. and Marintchev, Assen and Wagner, Gerhard. (2008) PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains. Proceedings of the National Academy of Sciences of the United States of America, 105 (9). pp. 3274-3279.

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Programmed Cell Death 4 (PDCD4) is a protein known to bind eukaryotic initiation factor 4A (eIF4A), inhibit translation initiation, and act as a tumor suppressor. PDCD4 contains two C-terminal MA3 domains, which are thought to be responsible for its inhibitory function. Here, we analyze the structures and inhibitory functions of these two PDCD4 MA3 domains by x-ray crystallography, NMR, and surface plasmon resonance. We show that both MA3 domains are structurally and functionally very similar and bind specifically to the eIF4A N-terminal domain (eIF4A-NTD) using similar binding interfaces. We found that the PDCD4 MA3 domains compete with the eIF4G MA3 domain and RNA for eIF4A binding. Our data provide evidence that PDCD4 inhibits translation initiation by displacing eIF4G and RNA from eIF4A. The PDCD4 MA3 domains act synergistically to form a tighter and more stable complex with eIF4A, which explains the need for two tandem MA3 domains.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller)
UniBasel Contributors:Hiller Odermatt, Sebastian
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Dec 2017 13:40
Deposited On:17 Aug 2016 09:02

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