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==Crystal structure of the human eIF4A1-ATP analog-RocA-polypurine RNA complex== | ==Crystal structure of the human eIF4A1-ATP analog-RocA-polypurine RNA complex== | ||
<StructureSection load='5zc9' size='340' side='right' caption='[[5zc9]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='5zc9' size='340' side='right'caption='[[5zc9]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5zc9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZC9 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5zc9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZC9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RCG:(1R,2R,3S,3aR,8bS)-6,8-dimethoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-1,8b-bis(oxidanyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide'>RCG</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RCG:(1R,2R,3S,3aR,8bS)-6,8-dimethoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-1,8b-bis(oxidanyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide'>RCG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zc9 OCA], [https://pdbe.org/5zc9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zc9 RCSB], [https://www.ebi.ac.uk/pdbsum/5zc9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zc9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/IF4A1_HUMAN IF4A1_HUMAN] ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.<ref>PMID:19153607</ref> <ref>PMID:19204291</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 19: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5zc9" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5zc9" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] | |||
*[[Helicase 3D structures|Helicase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: | [[Category: Ito T]] | ||
[[Category: | [[Category: Iwasaki S]] | ||
[[Category: | [[Category: Iwasaki W]] | ||
[[Category: | [[Category: Sakamoto A]] | ||
[[Category: | [[Category: Takahashi M]] | ||
Latest revision as of 11:51, 22 November 2023
Crystal structure of the human eIF4A1-ATP analog-RocA-polypurine RNA complexCrystal structure of the human eIF4A1-ATP analog-RocA-polypurine RNA complex
Structural highlights
FunctionIF4A1_HUMAN ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.[1] [2] Publication Abstract from PubMedA class of translation inhibitors, exemplified by the natural product rocaglamide A (RocA), isolated from Aglaia genus plants, exhibits antitumor activity by clamping eukaryotic translation initiation factor 4A (eIF4A) onto polypurine sequences in mRNAs. This unusual inhibitory mechanism raises the question of how the drug imposes sequence selectivity onto a general translation factor. Here, we determined the crystal structure of the human eIF4A1ATP analogRocApolypurine RNA complex. RocA targets the "bi-molecular cavity" formed characteristically by eIF4A1 and a sharply bent pair of consecutive purines in the RNA. Natural amino acid substitutions found in Aglaia eIF4As changed the cavity shape, leading to RocA resistance. This study provides an example of an RNA-sequence-selective interfacial inhibitor fitting into the space shaped cooperatively by protein and RNA with specific sequences. The Translation Inhibitor Rocaglamide Targets a Bimolecular Cavity between eIF4A and Polypurine RNA.,Iwasaki S, Iwasaki W, Takahashi M, Sakamoto A, Watanabe C, Shichino Y, Floor SN, Fujiwara K, Mito M, Dodo K, Sodeoka M, Imataka H, Honma T, Fukuzawa K, Ito T, Ingolia NT Mol Cell. 2018 Dec 18. pii: S1097-2765(18)30996-1. doi:, 10.1016/j.molcel.2018.11.026. PMID:30595437[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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