3U7X

Crystal structure of the human eIF4E-4EBP1 peptide complex without cap

「3SMU」から置き換えられました

3U7X の概要

• エントリーDOI: 10.2210/pdb3u7x/pdb
• 分子名称: Eukaryotic translation initiation factor 4E, Eukaryotic translation initiation factor 4E-binding protein 1, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: eif4e, 4ebp1, mrna export, structural genomics consortium, sgc, translation
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, P-body : P06730
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55360.25

構造登録者

Siddiqui, N.,Tempel, W.,Nedyalkova, L.,Wernimont, A.K.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Weigelt, J.,Borden, K.L.B.,Park, H.,Structural Genomics Consortium (SGC) (登録日: 2011-10-14, 公開日: 2011-11-02, 最終更新日: 2023-09-13)

主引用文献

Siddiqui, N.,Tempel, W.,Nedyalkova, L.,Volpon, L.,Wernimont, A.K.,Osborne, M.J.,Park, H.W.,Borden, K.L.
Structural Insights into the Allosteric Effects of 4EBP1 on the Eukaryotic Translation Initiation Factor eIF4E.
J.Mol.Biol., 415:781-792, 2012

PubMed Abstract: The eukaryotic translation initiation factor eIF4E plays key roles in cap-dependent translation and mRNA export. These functions rely on binding the 7-methyl-guanosine moiety (5'cap) on the 5'-end of all mRNAs. eIF4E is regulated by proteins such as eIF4G and eIF4E binding proteins (4EBPs) that bind the dorsal surface of eIF4E, distal to the cap binding site, and modulate cap binding activity. Both proteins increase the affinity of eIF4E for 5'cap. Our understanding of the allosteric effects and structural underpinnings of 4EBP1 or eIF4G binding can be advanced by obtaining structural data on cap-free eIF4E bound to one of these proteins. Here, we report the crystal structure of apo-eIF4E and cap-free eIF4E in complex with a 4EBP1 peptide. We also monitored 4EBP1 binding to cap-free eIF4E in solution using NMR. Together, these studies suggest that 4EBP1 transforms eIF4E into a cap-receptive state. NMR methods were also used to compare the allosteric routes activated by 4EBP1, eIF4G, and the arenavirus Z protein, a negative regulator of cap binding. We observed chemical shift perturbation at the dorsal binding site leading to alterations in the core of the protein, which were ultimately communicated to the unoccupied cap binding site of eIF4E. There were notable similarities between the routes taken by 4EBP1 and eIF4G and differences from the negative regulator Z. Thus, binding of 4EBP1 or eIF4G allosterically drives alterations throughout the protein that increase the affinity of eIF4E for the 5'cap.

PubMed: 22178476
DOI: 10.1016/j.jmb.2011.12.002

実験手法

X-RAY DIFFRACTION (2.1 Å)