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| | <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://proteopedia.org/fgij/fg.htm?mol=3EIQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3eiq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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 [https://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://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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</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=3eiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eiq OCA], [https://pdbe.org/3eiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eiq RCSB], [https://www.ebi.ac.uk/pdbsum/3eiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eiq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/PDCD4_MOUSE PDCD4_MOUSE]] Note=Decreases benign tumor development and malignant progression. | |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/PDCD4_MOUSE 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.<ref>PMID:12482958</ref> <ref>PMID:12894233</ref> <ref>PMID:16024603</ref> <ref>PMID:17060447</ref> | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Cheng, Z]] | + | [[Category: Cheng Z]] |
| - | [[Category: Loh, P G]] | + | [[Category: Loh PG]] |
| - | [[Category: Song, H]] | + | [[Category: Song H]] |
| - | [[Category: Anti-oncogene]]
| + | |
| - | [[Category: Antitumor protein]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Helicase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-antitumor protein complex]]
| + | |
| - | [[Category: Initiation factor]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Pdcd4]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein biosynthesis]]
| + | |
| - | [[Category: Rna-binding]]
| + | |
| - | [[Category: Translation]]
| + | |
| Structural highlights
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]
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
Pdcd4 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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
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