9q73

Crystal structure of T. brucei EIF4E5 in complex with EIF4G1 peptide

spinqualitylabelsall models 9q73, resolution 1.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9q73 is a 2 chain structure with sequence from Trypanosoma brucei brucei TREU927. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.66Å Ligands: 1BO, NA, PDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q38B99_TRYB2 Publication Abstract from PubMed 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. Selective eIF4E-eIF4G Pairing and Cap-4 Recognition Mechanisms in Trypanosomatids: Insights From EIF4E5-EIF4G1 and EIF4E6-EIF4G5 Complexes.,Penteado RF, Vichier-Guerre S, da Silva Pereira BM, Dugue L, Guerra Slompo EP, Assuncao de Matos TR, Pochet S, Zanchin NIT, Guimaraes BG J Mol Biol. 2026 Jan 15;438(2):169550. doi: 10.1016/j.jmb.2025.169550. Epub 2025 , Nov 18. PMID:41265746 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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