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2rg8

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Revision as of 20:30, 24 December 2014

Crystal Structure of Programmed for Cell Death 4 Middle MA3 domain

Structural highlights

2rg8 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Gene:	PDCD4, H731 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Palamarchuk A, Efanov A, Maximov V, Aqeilan RI, Croce CM, Pekarsky Y. Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. Cancer Res. 2005 Dec 15;65(24):11282-6. PMID:16357133 doi:10.1158/0008-5472.CAN-05-3469
↑ Yang HS, Matthews CP, Clair T, Wang Q, Baker AR, Li CC, Tan TH, Colburn NH. Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion. Mol Cell Biol. 2006 Feb;26(4):1297-306. PMID:16449643 doi:26/4/1297
↑ Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science. 2006 Oct 20;314(5798):467-71. PMID:17053147 doi:10.1126/science.1130276
↑ Suzuki C, Garces RG, Edmonds KA, Hiller S, Hyberts SG, Marintchev A, Wagner G. PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains. Proc Natl Acad Sci U S A. 2008 Feb 22;. PMID:18296639
↑ Loh PG, Yang HS, Walsh MA, Wang Q, Wang X, Cheng Z, Liu D, Song H. Structural basis for translational inhibition by the tumour suppressor Pdcd4. EMBO J. 2009 Feb 4;28(3):274-85. Epub 2009 Jan 15. PMID:19153607 doi:10.1038/emboj.2008.278
↑ Chang JH, Cho YH, Sohn SY, Choi JM, Kim A, Kim YC, Jang SK, Cho Y. Crystal structure of the eIF4A-PDCD4 complex. Proc Natl Acad Sci U S A. 2009 Feb 9. PMID:19204291
↑ Suzuki C, Garces RG, Edmonds KA, Hiller S, Hyberts SG, Marintchev A, Wagner G. PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains. Proc Natl Acad Sci U S A. 2008 Feb 22;. PMID:18296639

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rg8"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2rg8]] is a 2 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RG8 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-<tr><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='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><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD4, H731 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD4, H731 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rg8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rg8 RCSB], [http://www.ebi.ac.uk/pdbsum/2rg8 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rg8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rg8 RCSB], [http://www.ebi.ac.uk/pdbsum/2rg8 PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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]]
@@ Line 34: / Line 36: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Garces, R.]]
+[[Category: Garces, R]]
-[[Category: Suzuki, C.]]
+[[Category: Suzuki, C]]
-[[Category: Wagner, G.]]
+[[Category: Wagner, G]]
 [[Category: Anti-oncogene]]
 [[Category: Apoptosis]]

2rg8

From Proteopedia

Revision as of 20:30, 24 December 2014

Crystal Structure of Programmed for Cell Death 4 Middle MA3 domain

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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