4UEB

Complex of D. melanogaster eIF4E with a designed 4E-binding protein (Form II)

4UEB の概要

• エントリーDOI: 10.2210/pdb4ueb/pdb
• 関連するPDBエントリー: 4UE8 4UE9 4UEA 4UEC 4UED
• 分子名称: EUKARYOTIC TRANSLATION INITIATION FACTOR 4E, DESIGNED 4E-BP (3 entities in total)
• 機能のキーワード: translation, gene regulation, cap binding protein, 4e binding protein, translational repression
• 由来する生物種: DROSOPHILA MELANOGASTER (FRUIT FLY); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 79058.89

構造登録者

Peter, D.,Weichenrieder, O. (登録日: 2014-12-16, 公開日: 2015-02-25, 最終更新日: 2023-12-20)

主引用文献

Peter, D.,Igreja, C.,Weber, R.,Wohlbold, L.,Weiler, C.,Ebertsch, L.,Weichenrieder, O.,Izaurralde, E.
Molecular Architecture of 4E-BP Translational Inhibitors Bound to Eif4E.
Mol.Cell, 57:1074-, 2015

PubMed Abstract: The eIF4E-binding proteins (4E-BPs) represent a diverse class of translation inhibitors that are often deregulated in cancer cells. 4E-BPs inhibit translation by competing with eIF4G for binding to eIF4E through an interface that consists of canonical and non-canonical eIF4E-binding motifs connected by a linker. The lack of high-resolution structures including the linkers, which contain phosphorylation sites, limits our understanding of how phosphorylation inhibits complex formation. Furthermore, the binding mechanism of the non-canonical motifs is poorly understood. Here, we present structures of human eIF4E bound to 4E-BP1 and fly eIF4E bound to Thor, 4E-T, and eIF4G. These structures reveal architectural elements that are unique to 4E-BPs and provide insight into the consequences of phosphorylation. Guided by these structures, we designed and crystallized a 4E-BP mimic that shows increased repressive activity. Our studies pave the way for the rational design of 4E-BP mimics as therapeutic tools to decrease translation during oncogenic transformation.

PubMed: 25702871
DOI: 10.1016/J.MOLCEL.2015.01.017

実験手法

X-RAY DIFFRACTION (2.52 Å)