4dnn

From Proteopedia

(Difference between revisions)

Revision as of 02:39, 11 December 2016

Crystal structure of the Quaking Qua1 homodimerization domain

Structural highlights

4dnn is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:	Qk, Qk1, Qka1, Qki, Quaking (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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.

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Publication Abstract from PubMed

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.

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^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Saccomanno L, Loushin C, Jan E, Punkay E, Artzt K, Goodwin EB. The STAR protein QKI-6 is a translational repressor. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12605-10. PMID:10535969
↑ Li Z, Zhang Y, Li D, Feng Y. Destabilization and mislocalization of myelin basic protein mRNAs in quaking dysmyelination lacking the QKI RNA-binding proteins. J Neurosci. 2000 Jul 1;20(13):4944-53. PMID:10864952
↑ Pilotte J, Larocque D, Richard S. Nuclear translocation controlled by alternatively spliced isoforms inactivates the QUAKING apoptotic inducer. Genes Dev. 2001 Apr 1;15(7):845-58. PMID:11297509 doi:http://dx.doi.org/10.1101/gad.860301
↑ Noveroske JK, Lai L, Gaussin V, Northrop JL, Nakamura H, Hirschi KK, Justice MJ. Quaking is essential for blood vessel development. Genesis. 2002 Mar;32(3):218-30. PMID:11892011
↑ Wu JI, Reed RB, Grabowski PJ, Artzt K. Function of quaking in myelination: regulation of alternative splicing. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4233-8. Epub 2002 Mar 26. PMID:11917126 doi:http://dx.doi.org/10.1073/pnas.072090399
↑ Larocque D, Pilotte J, Chen T, Cloutier F, Massie B, Pedraza L, Couture R, Lasko P, Almazan G, Richard S. Nuclear retention of MBP mRNAs in the quaking viable mice. Neuron. 2002 Dec 5;36(5):815-29. PMID:12467586
↑ Li Z, Takakura N, Oike Y, Imanaka T, Araki K, Suda T, Kaname T, Kondo T, Abe K, Yamamura K. Defective smooth muscle development in qkI-deficient mice. Dev Growth Differ. 2003 Oct-Dec;45(5-6):449-62. PMID:14706070
↑ Larocque D, Galarneau A, Liu HN, Scott M, Almazan G, Richard S. Protection of p27(Kip1) mRNA by quaking RNA binding proteins promotes oligodendrocyte differentiation. Nat Neurosci. 2005 Jan;8(1):27-33. Epub 2004 Nov 28. PMID:15568022 doi:http://dx.doi.org/10.1038/nn1359
↑ Lakiza O, Frater L, Yoo Y, Villavicencio E, Walterhouse D, Goodwin EB, Iannaccone P. STAR proteins quaking-6 and GLD-1 regulate translation of the homologues GLI1 and tra-1 through a conserved RNA 3'UTR-based mechanism. Dev Biol. 2005 Nov 1;287(1):98-110. Epub 2005 Sep 29. PMID:16198329 doi:http://dx.doi.org/10.1016/j.ydbio.2005.08.038
↑ Bohnsack BL, Lai L, Northrop JL, Justice MJ, Hirschi KK. Visceral endoderm function is regulated by quaking and required for vascular development. Genesis. 2006 Feb;44(2):93-104. PMID:16470614 doi:http://dx.doi.org/10.1002/gene.20189
↑ Beuck C, Qu S, Fagg WS, Ares M Jr, Williamson JR. Structural analysis of the quaking homodimerization interface. J Mol Biol. 2012 Nov 9;423(5):766-81. doi: 10.1016/j.jmb.2012.08.027. Epub 2012, Sep 11. PMID:22982292 doi:http://dx.doi.org/10.1016/j.jmb.2012.08.027

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dnn"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the Quaking Qua1 homodimerization domain==
 <StructureSection load='4dnn' size='340' side='right' caption='[[4dnn]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DNN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4dnn]] is a 2 chain structure with sequence from [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=4DNN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DNN FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Qk, Qk1, Qka1, Qki, Quaking ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Qk, Qk1, Qka1, Qki, Quaking ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4dnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dnn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dnn RCSB], [http://www.ebi.ac.uk/pdbsum/4dnn PDBsum]</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=4dnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dnn OCA], [http://pdbe.org/4dnn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dnn RCSB], [http://www.ebi.ac.uk/pdbsum/4dnn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dnn ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4dnn" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Beuck, C]]
 [[Category: Qu, S]]

4dnn

From Proteopedia

Revision as of 02:39, 11 December 2016

Crystal structure of the Quaking Qua1 homodimerization domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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