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| | ==Crystal structure of the human 4EHP-4E-BP1 complex== | | ==Crystal structure of the human 4EHP-4E-BP1 complex== |
| - | <StructureSection load='5nvn' size='340' side='right' caption='[[5nvn]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5nvn' size='340' side='right'caption='[[5nvn]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5nvn]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NVN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NVN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5nvn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NVN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF4E2, EIF4EL3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF4EBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></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=5nvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nvn OCA], [http://pdbe.org/5nvn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nvn RCSB], [http://www.ebi.ac.uk/pdbsum/5nvn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nvn ProSAT]</span></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=5nvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nvn OCA], [https://pdbe.org/5nvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nvn RCSB], [https://www.ebi.ac.uk/pdbsum/5nvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nvn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IF4E2_HUMAN IF4E2_HUMAN]] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation (PubMed:9582349, PubMed:17368478, PubMed:25624349). Acts as a repressor of translation initiation (PubMed:22751931). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (By similarity).[UniProtKB:Q8BMB3]<ref>PMID:17368478</ref> <ref>PMID:22751931</ref> <ref>PMID:25624349</ref> <ref>PMID:9582349</ref> [[http://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN]] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</ref> | + | [https://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5nvn" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5nvn" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Peter, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Sandmeir, F]] | + | [[Category: Peter D]] |
| - | [[Category: Valkov, E]] | + | [[Category: Sandmeir F]] |
| - | [[Category: Cap-binding protein]] | + | [[Category: Valkov E]] |
| - | [[Category: Eif4e-binding protein 1]]
| + | |
| - | [[Category: Translation]]
| + | |
| - | [[Category: Translation initiation]]
| + | |
| - | [[Category: Translational regulation]]
| + | |
| Structural highlights
Function
4EBP1_HUMAN Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.[1]
Publication Abstract from PubMed
The eIF4E homologous protein (4EHP) is thought to repress translation by competing with eIF4E for binding to the 5' cap structure of specific mRNAs to which it is recruited through interactions with various proteins, including the GRB10-interacting GYF (glycine-tyrosine-phenylalanine domain) proteins 1 and 2 (GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP. Complementation assays in a GIGYF1/2-null cell line using structure-based mutants indicate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression. Our studies provide structural insights into the assembly of 4EHP-GIGYF1/2 repressor complexes and reveal that rather than merely facilitating 4EHP recruitment to transcripts, GIGYF1/2 proteins are required for repressive activity.
GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression.,Peter D, Weber R, Sandmeir F, Wohlbold L, Helms S, Bawankar P, Valkov E, Igreja C, Izaurralde E Genes Dev. 2017 Jun 1;31(11):1147-1161. doi: 10.1101/gad.299420.117. Epub 2017, Jul 11. PMID:28698298[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pause A, Belsham GJ, Gingras AC, Donze O, Lin TA, Lawrence JC Jr, Sonenberg N. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature. 1994 Oct 27;371(6500):762-7. PMID:7935836 doi:http://dx.doi.org/10.1038/371762a0
- ↑ Peter D, Weber R, Sandmeir F, Wohlbold L, Helms S, Bawankar P, Valkov E, Igreja C, Izaurralde E. GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression. Genes Dev. 2017 Jun 1;31(11):1147-1161. doi: 10.1101/gad.299420.117. Epub 2017, Jul 11. PMID:28698298 doi:http://dx.doi.org/10.1101/gad.299420.117
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