2zu6
From Proteopedia
(Difference between revisions)
| (5 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | [[Image:2zu6.png|left|200px]] | ||
| - | + | ==crystal structure of the eIF4A-PDCD4 complex== | |
| + | <StructureSection load='2zu6' size='340' side='right'caption='[[2zu6]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2zu6]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZU6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF4A1, DDX2A, EIF4A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PDCD4, H731 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2zu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu6 OCA], [https://pdbe.org/2zu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zu6 RCSB], [https://www.ebi.ac.uk/pdbsum/2zu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zu6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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> [[https://www.uniprot.org/uniprot/PDCD4_HUMAN PDCD4_HUMAN]] Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA (By similarity).<ref>PMID:16357133</ref> <ref>PMID:16449643</ref> <ref>PMID:17053147</ref> <ref>PMID:18296639</ref> <ref>PMID:19153607</ref> <ref>PMID:19204291</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zu/2zu6_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zu6 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the translation initiation factor eIF4A, an RNA helicase that catalyzes the unwinding of secondary structure at the 5'-untranslated region of mRNAs and controls the initiation of translation. Here, we determined the crystal structure of the human eIF4A and PDCD4 complex. The structure reveals that one molecule of PDCD4 binds to the two eIF4A molecules through the two different binding modes. While the two MA3 domains of PDCD4 bind to one eIF4A molecule, the C-terminal MA3 domain alone of the same PDCD4 also interacts with another eIF4A molecule. The eIF4A-PDCD4 complex structure suggests that the MA3 domain(s) of PDCD4 binds perpendicular to the interface of the two domains of eIF4A, preventing the domain closure of eIF4A and blocking the binding of RNA to eIF4A, both of which are required events in the function of eIF4A helicase. The structure, together with biochemical analyses, reveals insights into the inhibition mechanism of eIF4A by PDCD4 and provides a framework for designing chemicals that target eIF4A. | ||
| - | + | Crystal structure of the eIF4A-PDCD4 complex.,Chang JH, Cho YH, Sohn SY, Choi JM, Kim A, Kim YC, Jang SK, Cho Y Proc Natl Acad Sci U S A. 2009 Feb 9. PMID:19204291<ref>PMID:19204291</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2zu6" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| - | *[[Cell death protein|Cell death protein]] | + | *[[Cell death protein 3D structures|Cell death protein 3D structures]] |
| - | *[[Eukaryotic initiation factor|Eukaryotic initiation factor]] | + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: Chang, J H | + | [[Category: Human]] |
| - | [[Category: Cho, Y | + | [[Category: Large Structures]] |
| - | [[Category: Sohn, S Y | + | [[Category: Chang, J H]] |
| + | [[Category: Cho, Y]] | ||
| + | [[Category: Sohn, S Y]] | ||
[[Category: Anti-oncogene]] | [[Category: Anti-oncogene]] | ||
[[Category: Apoptosis]] | [[Category: Apoptosis]] | ||
[[Category: Atp-binding]] | [[Category: Atp-binding]] | ||
[[Category: Cell cycle]] | [[Category: Cell cycle]] | ||
| + | [[Category: Cytoplasm]] | ||
[[Category: Helicase]] | [[Category: Helicase]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
| Line 30: | Line 54: | ||
[[Category: Nucleus]] | [[Category: Nucleus]] | ||
[[Category: Phosphoprotein]] | [[Category: Phosphoprotein]] | ||
| + | [[Category: Polymorphism]] | ||
[[Category: Protein biosynthesis]] | [[Category: Protein biosynthesis]] | ||
[[Category: Protein-protein complex]] | [[Category: Protein-protein complex]] | ||
[[Category: Rna-binding]] | [[Category: Rna-binding]] | ||
Current revision
crystal structure of the eIF4A-PDCD4 complex
| |||||||||||
Categories: Human | Large Structures | Chang, J H | Cho, Y | Sohn, S Y | Anti-oncogene | Apoptosis | Atp-binding | Cell cycle | Cytoplasm | Helicase | Hydrolase | Initiation factor | Nucleotide-binding | Nucleus | Phosphoprotein | Polymorphism | Protein biosynthesis | Protein-protein complex | Rna-binding
