9q79: Difference between revisions
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==Crystal structure of T. cruzi EIF4E6 in complex with EIF4G5 peptide and cap-4== | |||
<StructureSection load='9q79' size='340' side='right'caption='[[9q79]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9q79]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi] and [https://en.wikipedia.org/wiki/Trypanosoma_cruzi_Dm28c Trypanosoma cruzi Dm28c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Q79 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Q79 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=LRM: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+(non-preferred+name)'>LRM</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9q79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9q79 OCA], [https://pdbe.org/9q79 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9q79 RCSB], [https://www.ebi.ac.uk/pdbsum/9q79 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9q79 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A2V2VTW2_TRYCR A0A2V2VTW2_TRYCR] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:41265746</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Guimaraes | <div class="pdbe-citations 9q79" style="background-color:#fffaf0;"></div> | ||
[[Category: Penteado | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Trypanosoma cruzi]] | |||
[[Category: Trypanosoma cruzi Dm28c]] | |||
[[Category: Guimaraes BG]] | |||
[[Category: Penteado RF]] | |||