3eiq: Difference between revisions
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==Crystal structure of Pdcd4-eIF4A== | ==Crystal structure of Pdcd4-eIF4A== | ||
<StructureSection load='3eiq' size='340' side='right' caption='[[3eiq]], [[Resolution|resolution]] 3.50Å' scene=''> | <StructureSection load='3eiq' size='340' side='right'caption='[[3eiq]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3eiq]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EIQ OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[3eiq]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EIQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3EIQ FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3eiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eiq OCA], [http://pdbe.org/3eiq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3eiq RCSB], [http://www.ebi.ac.uk/pdbsum/3eiq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3eiq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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==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 == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Lk3 transgenic mice]] | [[Category: Lk3 transgenic mice]] | ||
[[Category: Cheng, Z]] | [[Category: Cheng, Z]] | ||
Revision as of 13:23, 9 September 2020
Crystal structure of Pdcd4-eIF4ACrystal structure of Pdcd4-eIF4A
Structural highlights
Disease[PDCD4_MOUSE] Note=Decreases benign tumor development and malignant progression. Function[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.[1] [2] [PDCD4_MOUSE] 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.[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 PubMedPdcd4 is a tumour suppressor protein. It inhibits translation through interaction with translation initiator eIF4A, resulting in the suppression of neoplastic transformation and tumour invasion. Here, we present the crystal structures of an N-terminal-truncated Pdcd4 in free form and in complex with eIF4A. Upon binding to eIF4A, Pdcd4 undergoes a marked conformational change to form a heterotrimeric complex with eIF4A, with one Pdcd4 binding to two eIF4A molecules in two different modes. The binding of Pdcd4 to eIF4A is required to inhibit the enzymatic activity of eIF4A, translation initiation, and AP-1-dependent transcription. Both MA3 domains are required to efficiently compete with the C-terminal domain of eIF4G (eIF4Gc) for binding to eIF4A whereas a single MA3 is sufficient to inhibit translation. Our structural and mutational analyses reveal that Pdcd4 inhibits translation initiation by trapping eIF4A in an inactive conformation, and blocking its incorporation into the eIF4F complex. Structural basis for translational inhibition by the tumour suppressor Pdcd4.,Loh PG, Yang HS, Walsh MA, Wang Q, Wang X, Cheng Z, Liu D, Song H EMBO J. 2009 Feb 4;28(3):274-85. Epub 2009 Jan 15. PMID:19153607[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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