1sxl

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==RESONANCE ASSIGNMENTS AND SOLUTION STRUCTURE OF THE SECOND RNA-BINDING DOMAIN OF SEX-LETHAL DETERMINED BY MULTIDIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY==
==RESONANCE ASSIGNMENTS AND SOLUTION STRUCTURE OF THE SECOND RNA-BINDING DOMAIN OF SEX-LETHAL DETERMINED BY MULTIDIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY==
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<StructureSection load='1sxl' size='340' side='right'caption='[[1sxl]], [[NMR_Ensembles_of_Models | 17 NMR models]]' scene=''>
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<StructureSection load='1sxl' size='340' side='right'caption='[[1sxl]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1sxl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SXL FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1sxl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SXL FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SEX-LETHAL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1sxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sxl OCA], [https://pdbe.org/1sxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sxl RCSB], [https://www.ebi.ac.uk/pdbsum/1sxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sxl 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=1sxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sxl OCA], [https://pdbe.org/1sxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sxl RCSB], [https://www.ebi.ac.uk/pdbsum/1sxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sxl ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/SXL_DROME SXL_DROME]] Sex determination switch protein which controls sexual development by sex-specific splicing. Regulates dosage compensation in females by suppressing hyperactivation of X-linked genes. Expression of the embryo-specific isoform is under the control of primary sex-determining signal, which depends on the ratio of X chromosomes relative to autosomes (X:A ratio). Expression occurs in 2X:2A cells, but not in X:2A cells. The X:A ratio seems to be signaled by the relative concentration of the X-linked transcription factors SIS-A and SIS-B. As a result, the embryo-specific product is expressed early only in female embryos and specifies female-adult specific splicing; in the male where it is not expressed, the default splicing gives rise to a truncated non-functional protein. The female-specific isoform specifies the splicing of its own transcript, thereby initiating a positive autoregulatory feedback loop leading to female development pathway. The female-specific isoform controls the sex-specific splicing of transformer (TRA); acts as a translational repressor for male-specific lethal-2 (MSL-2) and prevents male-less (MLE), MSL-1 and MSL-3 proteins from associating with the female X chromosome.<ref>PMID:3144435</ref> <ref>PMID:1710769</ref> <ref>PMID:1547493</ref>
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[https://www.uniprot.org/uniprot/SXL_DROME SXL_DROME] Sex determination switch protein which controls sexual development by sex-specific splicing. Regulates dosage compensation in females by suppressing hyperactivation of X-linked genes. Expression of the embryo-specific isoform is under the control of primary sex-determining signal, which depends on the ratio of X chromosomes relative to autosomes (X:A ratio). Expression occurs in 2X:2A cells, but not in X:2A cells. The X:A ratio seems to be signaled by the relative concentration of the X-linked transcription factors SIS-A and SIS-B. As a result, the embryo-specific product is expressed early only in female embryos and specifies female-adult specific splicing; in the male where it is not expressed, the default splicing gives rise to a truncated non-functional protein. The female-specific isoform specifies the splicing of its own transcript, thereby initiating a positive autoregulatory feedback loop leading to female development pathway. The female-specific isoform controls the sex-specific splicing of transformer (TRA); acts as a translational repressor for male-specific lethal-2 (MSL-2) and prevents male-less (MLE), MSL-1 and MSL-3 proteins from associating with the female X chromosome.<ref>PMID:3144435</ref> <ref>PMID:1710769</ref> <ref>PMID:1547493</ref>
== 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=1sxl 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=1sxl ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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The RNA-binding protein Sex-lethal (Sxl) is a critical regulator of sexual differentiation and dosage compensation in Drosophila. This regulatory activity is a consequence of the ability of Sxl to bind uridine-rich RNA tracts involved in pre-mRNA splicing. Sxl contains two RNP consensus-type RNA-binding domains (RBDs). A structural study of a portion of Sxl (amino acids 199-294) containing the second RNA-binding domain (RBD-2) using multidimensional heteronuclear NMR is presented here. Nearly complete 1H, 13C, and 15N resonance assignments have been obtained from 15N- and 13C/15N-uniformly labeled protein. These assignments were used to analyze 3D 15N-separated NOESY and 13C/13C-separated 4D NOESY spectra which produced 494 total and 169 long-range NOE-derived distance restraints. Along with 41 backbone dihedral restraints, these distance restraints were employed to generate an intermediate-resolution family of calculated structures, which exhibits the beta alpha beta-beta alpha beta tertiary fold found in other RBD-containing proteins. The RMSD to the average structure for the backbone atoms of residues 11-93 is 1.55 +/- 0.30 A, while the RMSD for backbone atoms involved in secondary structure is 0.76 +/- 0.14 A. A capping box [Harper, E.T., &amp; Rose, G.D. (1993) Biochemistry 32, 7605-7609] was identified at the N-terminus of the first helix and has been characterized by short- and medium-range NOEs. Finally, significant structural similarities and differences between Sxl RBD-2 and other RBD-containing proteins are discussed.
 
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Resonance assignments and solution structure of the second RNA-binding domain of sex-lethal determined by multidimensional heteronuclear magnetic resonance.,Lee AL, Kanaar R, Rio DC, Wemmer DE Biochemistry. 1994 Nov 22;33(46):13775-86. PMID:7524663<ref>PMID:7524663</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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</div>
 
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<div class="pdbe-citations 1sxl" style="background-color:#fffaf0;"></div>
 
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Drome]]
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[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Kanaar, R]]
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[[Category: Kanaar R]]
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[[Category: Lee, A L]]
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[[Category: Lee AL]]
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[[Category: Rio, D C]]
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[[Category: Rio DC]]
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[[Category: Wemmer, D E]]
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[[Category: Wemmer DE]]
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[[Category: Rna binding protein]]
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[[Category: Rna-binding protein]]
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Revision as of 08:36, 1 May 2024

RESONANCE ASSIGNMENTS AND SOLUTION STRUCTURE OF THE SECOND RNA-BINDING DOMAIN OF SEX-LETHAL DETERMINED BY MULTIDIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

PDB ID 1sxl

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