2KZT

Structure of the Tandem MA-3 Region of Pdcd4

2KZT の概要

• エントリーDOI: 10.2210/pdb2kzt/pdb
• 分子名称: Programmed cell death protein 4 (2 entities in total)
• 機能のキーワード: pdcd4, ma-3, eif4a, heat, apoptosis
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q53EL6 Q61823
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32746.54

構造登録者

Waters, L.C.,Strong, S.L.,Oka, O.,Muskett, F.W.,Veverka, V.,Banerjee, S.,Schmedt, T.,Henry, A.J.,Klempnauer, K.H.,Carr, M.D. (登録日: 2010-06-24, 公開日: 2011-03-16, 最終更新日: 2024-05-01)

主引用文献

Waters, L.C.,Strong, S.L.,Ferlemann, E.,Oka, O.,Muskett, F.W.,Veverka, V.,Banerjee, S.,Schmedt, T.,Henry, A.J.,Klempnauer, K.H.,Carr, M.D.
Structure of the tandem MA-3 region of Pdcd4 protein and characterization of its interactions with eIF4A and eIF4G: molecular mechanisms of a tumor suppressor
J.Biol.Chem., 286:17270-17280, 2011

PubMed Abstract: One of the key regulatory points of translation initiation is recruitment of the 43S preinitation complex to the 5' mRNA cap by the eIF4F complex (eIF4A, eIF4E, and eIF4G). The tumor suppressor protein Pdcd4 has been shown to inhibit cap-dependent translation by interacting tightly with the RNA helicase eIF4A via its tandem MA-3 domains. The NMR studies reported here reveal a fairly extensive and well defined interface between the two MA-3 domains in solution, which appears to be stabilized by a network of interdomain salt bridges and hydrogen bonds, and reveals a unique orientation of the two domains. Characterization of the stoichiometry of the Pdcd4-eIF4A complex suggests that under physiological conditions Pdcd4 binds to a single molecule of eIF4A, which involves contacts with both Pdcd4 MA-3 domains. We also show that contacts mediated by a conserved acidic patch on the middle MA-3 domain of Pdcd4 are essential for forming a tight complex with eIF4A in vivo, whereas the equivalent region of the C-terminal MA-3 domain appears to have no role in complex formation in vivo. The formation of a 1:1 eIF4A-Pdcd4 complex in solution is consistent with the reported presence in vivo of only one molecule of eIF4A in the eIF4F complex. Pdcd4 has also been reported to interact directly with the middle region of eIF4G, however, we were unable to obtain any evidence for even a weak, transient direct interaction.

PubMed: 21454508
DOI: 10.1074/jbc.M110.166157

実験手法

SOLUTION NMR