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| ==Recognition of eIF4G by Rotavirus NSP3 reveals a basis for mRNA circularization== | | ==== |
| <StructureSection load='1lj2' size='340' side='right'caption='[[1lj2]], [[Resolution|resolution]] 2.38Å' scene=''> | | <StructureSection load='1lj2' size='340' side='right'caption='[[1lj2]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1lj2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Simian_11_rotavirus Simian 11 rotavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LJ2 FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AU:GOLD+ION'>AU</scene></td></tr> | | </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=1lj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lj2 OCA], [https://pdbe.org/1lj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lj2 RCSB], [https://www.ebi.ac.uk/pdbsum/1lj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lj2 ProSAT]</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=1lj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lj2 OCA], [http://pdbe.org/1lj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lj2 RCSB], [http://www.ebi.ac.uk/pdbsum/1lj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lj2 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Disease ==
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| [[http://www.uniprot.org/uniprot/IF4G1_HUMAN IF4G1_HUMAN]] Defects in EIF4G1 are the cause of Parkinson disease type 18 (PARK18) [MIM:[http://omim.org/entry/614251 614251]]. An autosomal dominant, late-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:21907011</ref>
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| == Function ==
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| [[http://www.uniprot.org/uniprot/NSP3_ROTS1 NSP3_ROTS1]] Involved in the shutoff of host protein synthesis. It is unclear whether it is required for the translation of viral mRNAs as well. Functions similarly to, and competes with the cellular poly(A)-binding protein PABPC1. Binds the conserved sequence 'GACC' at the 3' end of viral mRNAs and allows circularization of viral mRNAs in translation. Interacts with ZC3H7B/RoXaN and with the eukaryotic translation initiation factor eIF4G, using the same region employed by PABP-C1. NSP3 thus displaces PABPC1 from eIF4G, inhibiting the translation of cellular poly(A) mRNAs. Also responsible for the nuclear relocalization of PABPC1 upon rotavirus infection (By similarity). [[http://www.uniprot.org/uniprot/IF4G1_HUMAN IF4G1_HUMAN]] Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome.
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| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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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=1lj2 ConSurf]. | | </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=1lj2 ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Rotaviruses, segmented double-stranded RNA viruses, co-opt the eukaryotic translation machinery with the aid of nonstructural protein 3 (NSP3), a rotaviral functional homolog of the cellular poly(A) binding protein (PABP). NSP3 binds to viral mRNA 3' consensus sequences and circularizes mRNA via interactions with eIF4G. Here, we present the X-ray structure of the C-terminal domain of NSP3 (NSP3-C) recognizing a fragment of eIF4GI. Homodimerization of NSP3-C yields a symmetric, elongated, largely alpha-helical structure with two hydrophobic eIF4G binding pockets at the dimer interface. Site-directed mutagenesis and isothermal titration calorimetry documented that NSP3 and PABP use analogous eIF4G recognition strategies, despite marked differences in tertiary structure.
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| Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization.,Groft CM, Burley SK Mol Cell. 2002 Jun;9(6):1273-83. PMID:12086624<ref>PMID:12086624</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1lj2" style="background-color:#fffaf0;"></div>
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| ==See Also==
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| *[[Nonstructural protein 3D structures|Nonstructural protein 3D structures]]
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Simian 11 rotavirus]] | | [[Category: Z-disk]] |
| [[Category: Burley, S K]]
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| [[Category: Groft, C M]]
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| [[Category: Closed loop]]
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| [[Category: Coiled coil]]
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| [[Category: Eif4g]]
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| [[Category: Homodimer]]
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| [[Category: Mrna]]
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| [[Category: Nsp3]]
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| [[Category: Rotavirus]]
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| [[Category: Translation]]
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| [[Category: Viral protein- translation complex]]
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