2rg8

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[[Image:2rg8.jpg|left|200px]]
 
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{{Structure
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==Crystal Structure of Programmed for Cell Death 4 Middle MA3 domain==
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|PDB= 2rg8 |SIZE=350|CAPTION= <scene name='initialview01'>2rg8</scene>, resolution 1.8&Aring;
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<StructureSection load='2rg8' size='340' side='right'caption='[[2rg8]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Cl+Binding+Site+For+Residue+A+1'>AC1</scene>, <scene name='pdbsite=AC2:Cl+Binding+Site+For+Residue+B+2'>AC2</scene>, <scene name='pdbsite=AC3:Na+Binding+Site+For+Residue+B+3'>AC3</scene>, <scene name='pdbsite=AC4:Na+Binding+Site+For+Residue+A+4'>AC4</scene> and <scene name='pdbsite=AC5:Na+Binding+Site+For+Residue+B+5'>AC5</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=NA:SODIUM ION'>NA</scene>
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<table><tr><td colspan='2'>[[2rg8]] is a 2 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=2RG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RG8 FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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|GENE= PDCD4, H731 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<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>
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}}
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD4, H731 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rg8 OCA], [https://pdbe.org/2rg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rg8 RCSB], [https://www.ebi.ac.uk/pdbsum/2rg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rg8 ProSAT]</span></td></tr>
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'''Crystal Structure of Programmed for Cell Death 4 Middle MA3 domain'''
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</table>
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== Function ==
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[[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>
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==Overview==
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rg/2rg8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2rg8 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Programmed Cell Death 4 (PDCD4) is a protein known to bind eukaryotic initiation factor 4A (eIF4A), inhibit translation initiation, and act as a tumor suppressor. PDCD4 contains two C-terminal MA3 domains, which are thought to be responsible for its inhibitory function. Here, we analyze the structures and inhibitory functions of these two PDCD4 MA3 domains by x-ray crystallography, NMR, and surface plasmon resonance. We show that both MA3 domains are structurally and functionally very similar and bind specifically to the eIF4A N-terminal domain (eIF4A-NTD) using similar binding interfaces. We found that the PDCD4 MA3 domains compete with the eIF4G MA3 domain and RNA for eIF4A binding. Our data provide evidence that PDCD4 inhibits translation initiation by displacing eIF4G and RNA from eIF4A. The PDCD4 MA3 domains act synergistically to form a tighter and more stable complex with eIF4A, which explains the need for two tandem MA3 domains.
Programmed Cell Death 4 (PDCD4) is a protein known to bind eukaryotic initiation factor 4A (eIF4A), inhibit translation initiation, and act as a tumor suppressor. PDCD4 contains two C-terminal MA3 domains, which are thought to be responsible for its inhibitory function. Here, we analyze the structures and inhibitory functions of these two PDCD4 MA3 domains by x-ray crystallography, NMR, and surface plasmon resonance. We show that both MA3 domains are structurally and functionally very similar and bind specifically to the eIF4A N-terminal domain (eIF4A-NTD) using similar binding interfaces. We found that the PDCD4 MA3 domains compete with the eIF4G MA3 domain and RNA for eIF4A binding. Our data provide evidence that PDCD4 inhibits translation initiation by displacing eIF4G and RNA from eIF4A. The PDCD4 MA3 domains act synergistically to form a tighter and more stable complex with eIF4A, which explains the need for two tandem MA3 domains.
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==About this Structure==
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PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains.,Suzuki C, Garces RG, Edmonds KA, Hiller S, Hyberts SG, Marintchev A, Wagner G Proc Natl Acad Sci U S A. 2008 Feb 22;. PMID:18296639<ref>PMID:18296639</ref>
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2RG8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RG8 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains., Suzuki C, Garces RG, Edmonds KA, Hiller S, Hyberts SG, Marintchev A, Wagner G, Proc Natl Acad Sci U S A. 2008 Feb 22;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18296639 18296639]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2rg8" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Garces, R.]]
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[[Category: Suzuki, C.]]
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[[Category: Wagner, G.]]
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[[Category: CL]]
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[[Category: NA]]
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[[Category: anti-oncogene]]
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[[Category: apoptosis]]
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[[Category: cell cycle]]
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[[Category: cytoplasm]]
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[[Category: heat repeat]]
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[[Category: ma3 domain]]
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[[Category: nucleus]]
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[[Category: phosphorylation]]
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[[Category: polymorphism]]
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[[Category: rna-binding]]
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[[Category: translation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:35:49 2008''
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==See Also==
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*[[Cell death protein 3D structures|Cell death protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Human]]
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[[Category: Large Structures]]
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[[Category: Garces, R]]
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[[Category: Suzuki, C]]
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[[Category: Wagner, G]]
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[[Category: Anti-oncogene]]
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[[Category: Apoptosis]]
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[[Category: Cell cycle]]
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[[Category: Cytoplasm]]
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[[Category: Heat repeat]]
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[[Category: Ma3 domain]]
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[[Category: Nucleus]]
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[[Category: Phosphorylation]]
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[[Category: Polymorphism]]
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[[Category: Rna-binding]]
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[[Category: Translation]]

Current revision

Crystal Structure of Programmed for Cell Death 4 Middle MA3 domain

PDB ID 2rg8

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