4dnn

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[[Image:4dnn.jpg|left|200px]]
 
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{{STRUCTURE_4dnn| PDB=4dnn | SCENE= }}
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==Crystal structure of the Quaking Qua1 homodimerization domain==
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<StructureSection load='4dnn' size='340' side='right'caption='[[4dnn]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4dnn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DNN FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dnn OCA], [https://pdbe.org/4dnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dnn RCSB], [https://www.ebi.ac.uk/pdbsum/4dnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dnn ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/QKI_MOUSE QKI_MOUSE] Defects in Qki are the cause of quakingviable (qkv). Qkv is a spontaneous mutation resulting in hypomyelinization of the central and peripheral nervous systems. Mutant mice develop normally until postnatal day 10 when they display rapid tremors or 'quaking' that is especially pronounced in hindlimbs and experience convulsive tonic-clonic seizures as they mature. Mice with qkv specifically lack isoform 3 and isoform 4 in myelin-forming cells, while isoform 1 is lacking in oligodendrocytes of severely affected tracts. Mice with qkv also lack the Park2 gene product, suggesting that the absence of Park2 may also affect the phenotype.
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== Function ==
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[https://www.uniprot.org/uniprot/QKI_MOUSE QKI_MOUSE] RNA-binding protein that plays a central role in myelinization. Also required for visceral endoderm function and blood vessel development. Binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence. Acts by regulating pre-mRNA splicing, mRNA export, mRNA stability and protein translation, as well as cellular processes including apoptosis, cell cycle, glial cell fate and development. Required to protect and promote stability of mRNAs such as MBP and CDKN1B which promotes oligodendrocyte differentiation. Participates in mRNA transport by regulating the nuclear export of MBP mRNA. Isoform 1 is involved in regulation of mRNA splicing of MAG pre-mRNA by acting as a negative regulator of MAG exon 12 alternative splicing. Isoform 3 can induce apoptosis, while heterodimerization with other isoforms results in nuclear translocation of isoform 3 and suppression of apoptosis. Isoform 4 acts as a translational repressor for GLI1. May also play a role in smooth muscle development.<ref>PMID:10535969</ref> <ref>PMID:10864952</ref> <ref>PMID:11297509</ref> <ref>PMID:11892011</ref> <ref>PMID:11917126</ref> <ref>PMID:12467586</ref> <ref>PMID:14706070</ref> <ref>PMID:15568022</ref> <ref>PMID:16198329</ref> <ref>PMID:16470614</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Quaking (QkI) is a prototypical member of the STAR (signal transducer and activator of RNA) protein family, which plays key roles in posttranscriptional gene regulation by controlling mRNA translation, stability and splicing. QkI-5 has been shown to regulate mRNA expression in the central nervous system, but little is known about its roles in other tissues. STAR proteins function as dimers and bind to bipartite RNA sequences; however, the structural and functional roles of homodimerization and heterodimerization are still unclear. Here, we present the crystal structure of the QkI dimerization domain, which adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 (germ line development defective-1) and Sam68 (Src-associated protein during mitosis, 68kDa) but differs by an additional helix inserted in the dimer interface. Variability of the dimer interface residues likely ensures selective homodimerization by preventing association with non-cognate STAR family proteins in the cell. Mutations that inhibit dimerization also significantly impair RNA binding in vitro, alter QkI-5 protein levels and impair QkI function in a splicing assay in vivo. Together, our results indicate that a functional Qua1 homodimerization domain is required for QkI-5 function in mammalian cells.
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===Crystal structure of the Quaking Qua1 homodimerization domain===
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Structural analysis of the quaking homodimerization interface.,Beuck C, Qu S, Fagg WS, Ares M Jr, Williamson JR J Mol Biol. 2012 Nov 9;423(5):766-81. doi: 10.1016/j.jmb.2012.08.027. Epub 2012, Sep 11. PMID:22982292<ref>PMID:22982292</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==About this Structure==
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</div>
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[[4dnn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DNN OCA].
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<div class="pdbe-citations 4dnn" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Beuck, C.]]
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[[Category: Beuck C]]
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[[Category: Qu, S.]]
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[[Category: Qu S]]
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[[Category: Williamson, J R.]]
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[[Category: Williamson JR]]
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[[Category: Developmental protein]]
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[[Category: Helix-turn-helix]]
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[[Category: Hydrophobic homodimer interface]]
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[[Category: Perpendicular stacking of protomer]]
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[[Category: Rna-binding]]
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[[Category: Splicing]]
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[[Category: Translation regulation]]
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Current revision

Crystal structure of the Quaking Qua1 homodimerization domain

PDB ID 4dnn

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