9Q78

Crystal structure of T. cruzi EIF4E6 in complex with EIF4G5 peptide

9Q78 の概要

• エントリーDOI: 10.2210/pdb9q78/pdb
• 分子名称: Putative Eukaryotic translation initiation factor 4E type 6, Eukaryotic translation initiation factor 4 gamma 5 (3 entities in total)
• 機能のキーワード: translation initiation factor, eif4e family, eif4e6, eif4g5, translation
• 由来する生物種: Trypanosoma cruzi Dm28c; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 108431.18

構造登録者

Penteado, R.F.,Guimaraes, B.G. (登録日: 2025-08-22, 公開日: 2026-01-21)

主引用文献

Penteado, R.F.,Vichier-Guerre, S.,da Silva Pereira, B.M.,Dugue, L.,Guerra Slompo, E.P.,Assuncao de Matos, T.R.,Pochet, S.,Zanchin, N.I.T.,Guimaraes, B.G.
Selective eIF4E-eIF4G Pairing and Cap-4 Recognition Mechanisms in Trypanosomatids: Insights From EIF4E5-EIF4G1 and EIF4E6-EIF4G5 Complexes.
J.Mol.Biol., 438:169550-169550, 2026

PubMed Abstract: Translation initiation in eukaryotes is a highly regulated process involving the assembly of several transient protein complexes. A key step in this process is recognition of the mRNA 5' cap structure by the initiation factor eIF4E, a core component of the eIF4F complex. In trypanosomatids, this mechanism diverges from canonical eukaryotic systems, featuring five distinct eIF4F-like complexes formed through specific pairings of eIF4E and eIF4G homologs. Additionally, trypanosomatid mRNAs exhibit a unique hypermethylated cap-4 structure at the 5' end. To elucidate the molecular basis of selective eIF4E-eIF4G interactions and the modulation of cap binding upon eIF4G engagement, we determined high-resolution crystal structures of EIF4E5-EIF4G1 complexes from Trypanosoma brucei and T. cruzi, and the EIF4E6-EIF4G5 complex from T. cruzi. These structural studies, supported by biophysical analyses in the presence and absence of a cap-4 analog, reveal key determinants of cap recognition associated with cap-4 structural flexibility and plasticity in the cap-binding pockets. We observe conformational rearrangements upon eIF4G binding and propose a relationship between these structural changes and increased cap-4 affinity. In addition, comparative structural analysis of the EIF4E5-EIF4G1 and EIF4E6-EIF4G5 complexes offers atomic-level insights into the molecular determinants of specificity that govern selective eIF4E-eIF4G pairings in trypanosomatids.

PubMed: 41265746
DOI: 10.1016/j.jmb.2025.169550

実験手法

X-RAY DIFFRACTION (2.1 Å)