5NVM

Crystal structure of the human 4EHP-GIGYF2 complex lacking the auxiliary sequences

5NVM の概要

• エントリーDOI: 10.2210/pdb5nvm/pdb
• 分子名称: Eukaryotic translation initiation factor 4E type 2, GRB10-interacting GYF protein 2, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: translational regulation, cap-binding protein, 4ehp-binding protein, grb10-interacting gyf protein 2, translation
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 54375.87

構造登録者

Peter, D.,Valkov, E. (登録日: 2017-05-04, 公開日: 2017-07-26, 最終更新日: 2024-01-17)

主引用文献

Peter, D.,Weber, R.,Sandmeir, F.,Wohlbold, L.,Helms, S.,Bawankar, P.,Valkov, E.,Igreja, C.,Izaurralde, E.
GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression.
Genes Dev., 31:1147-1161, 2017

PubMed Abstract: The eIF4E homologous protein (4EHP) is thought to repress translation by competing with eIF4E for binding to the 5' cap structure of specific mRNAs to which it is recruited through interactions with various proteins, including the GRB10-interacting GYF (glycine-tyrosine-phenylalanine domain) proteins 1 and 2 (GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP. Complementation assays in a GIGYF1/2-null cell line using structure-based mutants indicate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression. Our studies provide structural insights into the assembly of 4EHP-GIGYF1/2 repressor complexes and reveal that rather than merely facilitating 4EHP recruitment to transcripts, GIGYF1/2 proteins are required for repressive activity.

PubMed: 28698298
DOI: 10.1101/gad.299420.117

実験手法

X-RAY DIFFRACTION (2 Å)