3EIQ

Crystal structure of Pdcd4-eIF4A

3EIQ の概要

• エントリーDOI: 10.2210/pdb3eiq/pdb
• 分子名称: Eukaryotic initiation factor 4A-I, Programmed cell death protein 4 (2 entities in total)
• 機能のキーワード: pdcd4, anti-oncogene, apoptosis, cell cycle, nucleus, phosphoprotein, rna-binding, atp-binding, helicase, hydrolase, initiation factor, nucleotide-binding, protein biosynthesis, antitumor protein, translation, hydrolase-antitumor protein complex, hydrolase/antitumor protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P60842
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 133827.52

構造登録者

Loh, P.G.,Cheng, Z.,Song, H. (登録日: 2008-09-17, 公開日: 2009-02-24, 最終更新日: 2023-11-01)

主引用文献

Loh, P.G.,Yang, H.S.,Walsh, M.A.,Wang, Q.,Wang, X.,Cheng, Z.,Liu, D.,Song, H.
Structural basis for translational inhibition by the tumour suppressor Pdcd4
Embo J., 28:274-285, 2009

PubMed Abstract: Pdcd4 is a tumour suppressor protein. It inhibits translation through interaction with translation initiator eIF4A, resulting in the suppression of neoplastic transformation and tumour invasion. Here, we present the crystal structures of an N-terminal-truncated Pdcd4 in free form and in complex with eIF4A. Upon binding to eIF4A, Pdcd4 undergoes a marked conformational change to form a heterotrimeric complex with eIF4A, with one Pdcd4 binding to two eIF4A molecules in two different modes. The binding of Pdcd4 to eIF4A is required to inhibit the enzymatic activity of eIF4A, translation initiation, and AP-1-dependent transcription. Both MA3 domains are required to efficiently compete with the C-terminal domain of eIF4G (eIF4Gc) for binding to eIF4A whereas a single MA3 is sufficient to inhibit translation. Our structural and mutational analyses reveal that Pdcd4 inhibits translation initiation by trapping eIF4A in an inactive conformation, and blocking its incorporation into the eIF4F complex.

PubMed: 19153607
DOI: 10.1038/emboj.2008.278

実験手法

X-RAY DIFFRACTION (3.5 Å)