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| | ==SEX-LETHAL RBD1, NMR, MINIMIZED AVERAGE STRUCTURE== | | ==SEX-LETHAL RBD1, NMR, MINIMIZED AVERAGE STRUCTURE== |
| - | <StructureSection load='2sxl' size='340' side='right'caption='[[2sxl]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='2sxl' size='340' side='right'caption='[[2sxl]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2sxl]] 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=2SXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2SXL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2sxl]] 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=2SXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2SXL FirstGlance]. <br> |
| - | </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> | + | </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=2sxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2sxl OCA], [https://pdbe.org/2sxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2sxl RCSB], [https://www.ebi.ac.uk/pdbsum/2sxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2sxl ProSAT], [https://www.topsan.org/Proteins/RSGI/2sxl TOPSAN]</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=2sxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2sxl OCA], [https://pdbe.org/2sxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2sxl RCSB], [https://www.ebi.ac.uk/pdbsum/2sxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2sxl ProSAT], [https://www.topsan.org/Proteins/RSGI/2sxl TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Inoue, M]] | + | [[Category: Inoue M]] |
| - | [[Category: Kigawa, T]] | + | [[Category: Kigawa T]] |
| - | [[Category: Muto, Y]] | + | [[Category: Muto Y]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Sakamoto H]] |
| - | [[Category: Sakamoto, H]] | + | [[Category: Shimura Y]] |
| - | [[Category: Shimura, Y]] | + | [[Category: Takio K]] |
| - | [[Category: Takio, K]] | + | [[Category: Yokoyama S]] |
| - | [[Category: Yokoyama, S]] | + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Rna-binding domain]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| Structural highlights
Function
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.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Sex-lethal (Sxl) protein from Drosophila melanogaster has two RNA-binding domains (RBDs). As the amino-terminal RBD (RBD1) of the Sxl protein exhibits low sequence homology to the typical RBDs, particularly at the putative functional residues, it was difficult to unambiguously locate the RNP1 and RNP2 motifs. Therefore, in the present study, we defined the amino and carboxy-terminal borders of the first RNA-binding domain (RBD1) of the Sxl protein by limited tryptic digestion. By replacement of Phe166 by Tyr, we constructed a highly soluble mutant, which exhibits the same RNA-binding properties as those of the wild-type. Using this mutant protein, we performed NMR measurements, and elucidated the secondary and tertiary structures of the Sxl RBD1 in solution. The betaalphabetabetaalphabeta folding pattern is conserved in the solution structure of the Sxl RBD1, as in other reported RBD structures. This allowed us to identify both the RNP1 and RNP2 motifs of the Sxl RBD1 unambiguously. Intriguingly, the RNP2 motif of the Sxl RBD1 has an Ile residue at the second position, which is generally occupied by an aromatic amino acid residue in RBDs and has been suggested to be involved in their RNA binding. Furthermore, the loop region between beta2 and beta3 of the Sxl RBD1 has an exceptional cluster of aromatic amino acid residues, in place of the normal basic amino acid cluster. In contrast, the second RBD of Sxl does not exhibit these characteristic features.
A characteristic arrangement of aromatic amino acid residues in the solution structure of the amino-terminal RNA-binding domain of Drosophila sex-lethal.,Inoue M, Muto Y, Sakamoto H, Kigawa T, Takio K, Shimura Y, Yokoyama S J Mol Biol. 1997 Sep 12;272(1):82-94. PMID:9299339[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bell LR, Maine EM, Schedl P, Cline TW. Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins. Cell. 1988 Dec 23;55(6):1037-46. PMID:3144435
- ↑ Samuels ME, Schedl P, Cline TW. The complex set of late transcripts from the Drosophila sex determination gene sex-lethal encodes multiple related polypeptides. Mol Cell Biol. 1991 Jul;11(7):3584-602. PMID:1710769
- ↑ Keyes LN, Cline TW, Schedl P. The primary sex determination signal of Drosophila acts at the level of transcription. Cell. 1992 Mar 6;68(5):933-43. PMID:1547493
- ↑ Inoue M, Muto Y, Sakamoto H, Kigawa T, Takio K, Shimura Y, Yokoyama S. A characteristic arrangement of aromatic amino acid residues in the solution structure of the amino-terminal RNA-binding domain of Drosophila sex-lethal. J Mol Biol. 1997 Sep 12;272(1):82-94. PMID:9299339 doi:10.1006/jmbi.1997.1213
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