2RG8

Crystal Structure of Programmed for Cell Death 4 Middle MA3 domain

2RG8 の概要

• エントリーDOI: 10.2210/pdb2rg8/pdb
• 分子名称: Programmed cell death protein 4, CHLORIDE ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: ma3 domain, heat repeats, anti-oncogene, apoptosis, cell cycle, cytoplasm, nucleus, phosphorylation, polymorphism, rna-binding, translation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : Q53EL6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36143.45

構造登録者

Garces, R.,Suzuki, C.,Wagner, G. (登録日: 2007-10-03, 公開日: 2008-03-04, 最終更新日: 2024-11-13)

主引用文献

Suzuki, C.,Garces, R.G.,Edmonds, K.A.,Hiller, S.,Hyberts, S.G.,Marintchev, A.,Wagner, G.
PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains.
Proc.Natl.Acad.Sci.Usa, 105:3274-3279, 2008

PubMed Abstract: 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.

PubMed: 18296639
DOI: 10.1073/pnas.0712235105

実験手法

X-RAY DIFFRACTION (1.8 Å)