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| ==Solution structure of the PWI motif from SRm160== | | ==Solution structure of the PWI motif from SRm160== |
- | <StructureSection load='1mp1' size='340' side='right'caption='[[1mp1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1mp1' size='340' side='right'caption='[[1mp1]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[1mp1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MP1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1mp1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MP1 FirstGlance]. <br> |
- | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRm160 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1mp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mp1 OCA], [https://pdbe.org/1mp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mp1 RCSB], [https://www.ebi.ac.uk/pdbsum/1mp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mp1 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=1mp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mp1 OCA], [https://pdbe.org/1mp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mp1 RCSB], [https://www.ebi.ac.uk/pdbsum/1mp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mp1 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[https://www.uniprot.org/uniprot/SRRM1_HUMAN SRRM1_HUMAN]] Part of pre- and post-splicing multiprotein mRNP complexes. Involved in numerous pre-mRNA processing events. Promotes constitutive and exonic splicing enhancer (ESE)-dependent splicing activation by bridging together sequence-specific (SR family proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP (SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA 3'-end cleavage independently of the formation of an exon junction complex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream of exon-exon junctions. Binds RNA and DNA with low sequence specificity and has similar preference for either double- or single-stranded nucleic acid substrates.<ref>PMID:9531537</ref> <ref>PMID:10339552</ref> <ref>PMID:10668804</ref> <ref>PMID:11739730</ref> <ref>PMID:12944400</ref> <ref>PMID:12600940</ref>
| + | [https://www.uniprot.org/uniprot/SRRM1_HUMAN SRRM1_HUMAN] Part of pre- and post-splicing multiprotein mRNP complexes. Involved in numerous pre-mRNA processing events. Promotes constitutive and exonic splicing enhancer (ESE)-dependent splicing activation by bridging together sequence-specific (SR family proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP (SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA 3'-end cleavage independently of the formation of an exon junction complex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream of exon-exon junctions. Binds RNA and DNA with low sequence specificity and has similar preference for either double- or single-stranded nucleic acid substrates.<ref>PMID:9531537</ref> <ref>PMID:10339552</ref> <ref>PMID:10668804</ref> <ref>PMID:11739730</ref> <ref>PMID:12944400</ref> <ref>PMID:12600940</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: Human]] | + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
- | [[Category: Blencowe, B J]] | + | [[Category: Blencowe BJ]] |
- | [[Category: Bowman, J]] | + | [[Category: Bowman J]] |
- | [[Category: Cox, B]] | + | [[Category: Cox B]] |
- | [[Category: Graveley, B R]] | + | [[Category: Graveley BR]] |
- | [[Category: Lambermon, M]] | + | [[Category: Lambermon M]] |
- | [[Category: Lu, Y]] | + | [[Category: Lu Y]] |
- | [[Category: McCracken, S]] | + | [[Category: McCracken S]] |
- | [[Category: Pineda-Lucena, A]] | + | [[Category: Pineda-Lucena A]] |
- | [[Category: Szymczyna, B R]] | + | [[Category: Szymczyna BR]] |
- | [[Category: Four helix bundle]]
| + | |
- | [[Category: Rna binding protein]]
| + | |
| Structural highlights
Function
SRRM1_HUMAN Part of pre- and post-splicing multiprotein mRNP complexes. Involved in numerous pre-mRNA processing events. Promotes constitutive and exonic splicing enhancer (ESE)-dependent splicing activation by bridging together sequence-specific (SR family proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP (SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA 3'-end cleavage independently of the formation of an exon junction complex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream of exon-exon junctions. Binds RNA and DNA with low sequence specificity and has similar preference for either double- or single-stranded nucleic acid substrates.[1] [2] [3] [4] [5] [6]
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 PWI motif is a highly conserved domain of unknown function in the SRm160 splicing and 3'-end cleavage-stimulatory factor, as well as in several other known or putative pre-mRNA processing components. We show here that the PWI motif is a new type of RNA/DNA-binding domain that has an equal preference for single- and double-stranded nucleic acids. Deletion of the motif prevents SRm160 from binding RNA and stimulating 3'-end cleavage, and its substitution with a heterologous RNA-binding domain restores these functions. The NMR solution structure of the SRm160-PWI motif reveals a novel, four-helix bundle and represents the first example of an alpha-helical fold that can bind single-stranded (ss)RNA. Structure-guided mutagenesis indicates that the same surface is involved in RNA and DNA binding and requires the cooperative action of a highly conserved, adjacent basic region. Thus, the PWI motif is a novel type of nucleic acid-binding domain that likely has multiple important functions in pre-mRNA processing, including SRm160-dependent stimulation of 3'-end formation.
Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing.,Szymczyna BR, Bowman J, McCracken S, Pineda-Lucena A, Lu Y, Cox B, Lambermon M, Graveley BR, Arrowsmith CH, Blencowe BJ Genes Dev. 2003 Feb 15;17(4):461-75. PMID:12600940[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Blencowe BJ, Issner R, Nickerson JA, Sharp PA. A coactivator of pre-mRNA splicing. Genes Dev. 1998 Apr 1;12(7):996-1009. PMID:9531537
- ↑ Eldridge AG, Li Y, Sharp PA, Blencowe BJ. The SRm160/300 splicing coactivator is required for exon-enhancer function. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6125-30. PMID:10339552
- ↑ Blencowe BJ, Bauren G, Eldridge AG, Issner R, Nickerson JA, Rosonina E, Sharp PA. The SRm160/300 splicing coactivator subunits. RNA. 2000 Jan;6(1):111-20. PMID:10668804
- ↑ McCracken S, Lambermon M, Blencowe BJ. SRm160 splicing coactivator promotes transcript 3'-end cleavage. Mol Cell Biol. 2002 Jan;22(1):148-60. PMID:11739730
- ↑ McCracken S, Longman D, Johnstone IL, Caceres JF, Blencowe BJ. An evolutionarily conserved role for SRm160 in 3'-end processing that functions independently of exon junction complex formation. J Biol Chem. 2003 Nov 7;278(45):44153-60. Epub 2003 Aug 27. PMID:12944400 doi:http://dx.doi.org/10.1074/jbc.M306856200
- ↑ Szymczyna BR, Bowman J, McCracken S, Pineda-Lucena A, Lu Y, Cox B, Lambermon M, Graveley BR, Arrowsmith CH, Blencowe BJ. Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing. Genes Dev. 2003 Feb 15;17(4):461-75. PMID:12600940 doi:10.1101/gad.1060403
- ↑ Szymczyna BR, Bowman J, McCracken S, Pineda-Lucena A, Lu Y, Cox B, Lambermon M, Graveley BR, Arrowsmith CH, Blencowe BJ. Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing. Genes Dev. 2003 Feb 15;17(4):461-75. PMID:12600940 doi:10.1101/gad.1060403
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