9Q72

Trypanosoma brucei EIF4E5 translation initiation factor in complex with cap-4

Summary for 9Q72

• Entry DOI: 10.2210/pdb9q72/pdb
• Descriptor: Eukaryotic translation initiation factor 4E type 5, 2-amino-9-[(2R,3R,4S,5R)-5-({[(R)-{[(R)-{[(S)-({(2R,3R,4R,5R)-3-{[(R)-{[(2R,3R,4R,5R)-3-{[(S)-{[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-{[(S)-hydroxy{[(2R,3R,4R,5R)-3-hydroxy-4-methoxy-5-(3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methoxy}phosphoryl]oxy}-4-methoxytetrahydrofuran-2-yl]methoxy}(hydroxy)phosphoryl]oxy}-5-(6-amino-9H-purin-9-yl)-4-methoxytetrahydrofuran-2-yl]methoxy}(hydroxy)phosphoryl]oxy}-5-[6-(dimethylamino)-9H-purin-9-yl]-4-methoxytetrahydrofuran-2-yl}methoxy)(hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl]oxy}methyl)-3,4-dihydroxytetrahydrofuran-2-yl]-7-methyl-6-oxo-6,9-dihydro-3H-purin-7-ium, IMIDAZOLE, ... (7 entities in total)
• Functional Keywords: rna binding protein, translation initiation factor, trypanosomatids, cap-4, translation
• Biological source: Trypanosoma brucei brucei TREU927
• Total number of polymer chains: 1
• Total formula weight: 26242.56

Authors

Penteado, R.F.,Guimaraes, B.G. (deposition date: 2025-08-22, release date: 2025-11-26, Last modification date: 2026-01-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.25 Å)