6O7Y

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

Summary for 6O7Y

• Entry DOI: 10.2210/pdb6o7y/pdb
• Related: 6O7Z 6O80
• Descriptor: Putative 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, SULFATE ION, ... (4 entities in total)
• Functional Keywords: rna binding protein, translation initiation factor, trypanosomatids, cap-4
• Biological source: Trypanosoma cruzi
• Total number of polymer chains: 1
• Total formula weight: 27286.95

Authors

Guimaraes, B.G.,Reolon, L.W. (deposition date: 2019-03-08, release date: 2019-05-01, Last modification date: 2024-03-13)

Primary citation

Reolon, L.W.,Vichier-Guerre, S.,de Matos, B.M.,Dugue, L.,Assuncao, T.R.D.S.,Zanchin, N.I.T.,Pochet, S.,Guimaraes, B.G.
Crystal structure of the Trypanosoma cruzi EIF4E5 translation factor homologue in complex with mRNA cap-4.
Nucleic Acids Res., 47:5973-5987, 2019

PubMed Abstract: Association of the initiation factor eIF4E with the mRNA cap structure is a key step for translation. Trypanosomatids present six eIF4E homologues, showing a low conservation and also differing significantly from the IF4Es of multicellular eukaryotes. On the mRNA side, while in most eukaryotes the mRNA contains cap-0 (7-methyl-GTP), the trypanosomatid mRNA features a cap-4, which is formed by a cap-0, followed by the AACU sequence containing 2'-O-ribose methylations and base methylations on nucleotides 1 and 4. The studies on eIF4E-cap-4 interaction have been hindered by the difficulty to synthesize this rather elaborated cap-4 sequence. To overcome this problem, we applied a liquid-phase oligonucleotide synthesis strategy and describe for the first time the crystal structure of a trypanosomatid eIF4E (T. cruzi EIF4E5) in complex with cap-4. The TcEIF4E5-cap-4 structure allowed a detailed description of the binding mechanism, revealing the interaction mode for the AACU sequence, with the bases packed in a parallel stacking conformation and involved, together with the methyl groups, in hydrophobic contacts with the protein. This binding mechanism evidences a distinct cap interaction mode in comparison with previously described eIF4E structures and may account for the difference of TcEIF4E5-cap-4 dissociation constant in comparison with other eIF4E homologues.

PubMed: 31066441
DOI: 10.1093/nar/gkz339

Experimental method

X-RAY DIFFRACTION (2.2 Å)