2ZU6

crystal structure of the eIF4A-PDCD4 complex

2ZU6 の概要

• エントリーDOI: 10.2210/pdb2zu6/pdb
• 分子名称: Eukaryotic initiation factor 4A-I, Programmed cell death protein 4, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: protein-protein complex, atp-binding, helicase, hydrolase, initiation factor, nucleotide-binding, protein biosynthesis, rna-binding, anti-oncogene, apoptosis, cell cycle, cytoplasm, nucleus, phosphoprotein, polymorphism
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: Q53EL6
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 246920.52

構造登録者

Cho, Y.,Chang, J.H.,Sohn, S.Y. (登録日: 2008-10-13, 公開日: 2009-02-24, 最終更新日: 2011-07-13)

主引用文献

Chang, J.H.,Cho, Y.H.,Sohn, S.Y.,Choi, J.M.,Kim, A.,Kim, Y.C.,Jang, S.K.,Cho, Y.
Crystal structure of the eIF4A-PDCD4 complex
Proc.Natl.Acad.Sci.Usa, 106:3148-3153, 2009

PubMed Abstract: Tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the translation initiation factor eIF4A, an RNA helicase that catalyzes the unwinding of secondary structure at the 5'-untranslated region of mRNAs and controls the initiation of translation. Here, we determined the crystal structure of the human eIF4A and PDCD4 complex. The structure reveals that one molecule of PDCD4 binds to the two eIF4A molecules through the two different binding modes. While the two MA3 domains of PDCD4 bind to one eIF4A molecule, the C-terminal MA3 domain alone of the same PDCD4 also interacts with another eIF4A molecule. The eIF4A-PDCD4 complex structure suggests that the MA3 domain(s) of PDCD4 binds perpendicular to the interface of the two domains of eIF4A, preventing the domain closure of eIF4A and blocking the binding of RNA to eIF4A, both of which are required events in the function of eIF4A helicase. The structure, together with biochemical analyses, reveals insights into the inhibition mechanism of eIF4A by PDCD4 and provides a framework for designing chemicals that target eIF4A.

PubMed: 19204291
DOI: 10.1073/pnas.0808275106

実験手法

X-RAY DIFFRACTION (2.8 Å)