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| | ==Solution NMR Structure of the First Domain of KSRP== | | ==Solution NMR Structure of the First Domain of KSRP== |
| - | <StructureSection load='2opu' size='340' side='right' caption='[[2opu]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''> | + | <StructureSection load='2opu' size='340' side='right'caption='[[2opu]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2opu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OPU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OPU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2opu]] 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=2OPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OPU FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hh3|2hh3]], [[2hh2|2hh2]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2hh3|2hh3]], [[2hh2|2hh2]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KHSRP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KHSRP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2opu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2opu OCA], [http://pdbe.org/2opu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2opu RCSB], [http://www.ebi.ac.uk/pdbsum/2opu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2opu 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=2opu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2opu OCA], [https://pdbe.org/2opu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2opu RCSB], [https://www.ebi.ac.uk/pdbsum/2opu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2opu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FUBP2_HUMAN FUBP2_HUMAN]] Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.<ref>PMID:9136930</ref> <ref>PMID:8940189</ref> <ref>PMID:11003644</ref> | + | [[https://www.uniprot.org/uniprot/FUBP2_HUMAN FUBP2_HUMAN]] Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.<ref>PMID:9136930</ref> <ref>PMID:8940189</ref> <ref>PMID:11003644</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Diaz-Moreno, I]] | | [[Category: Diaz-Moreno, I]] |
| | [[Category: Garcia-Mayoral, M F]] | | [[Category: Garcia-Mayoral, M F]] |
| Structural highlights
Function
[FUBP2_HUMAN] Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.[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 AU-rich element (ARE)-mediated mRNA-degradation activity of the RNA binding K-homology splicing regulator protein (KSRP) is regulated by phosphorylation of a serine within its N-terminal KH domain (KH1). In the cell, phosphorylation promotes the interaction of KSRP and 14-3-3zeta protein and impairs the ability of KSRP to promote the degradation of its RNA targets. Here we examine the molecular details of this mechanism. We report that phosphorylation leads to the unfolding of the structurally atypical and unstable KH1, creating a site for 14-3-3zeta binding. Using this site, 14-3-3zeta discriminates between phosphorylated and unphosphorylated KH1, driving the nuclear localization of KSRP. 14-3-3zeta -KH1 interaction regulates the mRNA-decay activity of KSRP by sequestering the protein in a separate functional pool. This study demonstrates how an mRNA-degradation pathway is connected to extracellular signaling networks through the reversible unfolding of a protein domain.
Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding.,Diaz-Moreno I, Hollingworth D, Frenkiel TA, Kelly G, Martin S, Howell S, Garcia-Mayoral M, Gherzi R, Briata P, Ramos A Nat Struct Mol Biol. 2009 Mar;16(3):238-46. Epub 2009 Feb 8. PMID:19198587[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Min H, Turck CW, Nikolic JM, Black DL. A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer. Genes Dev. 1997 Apr 15;11(8):1023-36. PMID:9136930
- ↑ Davis-Smyth T, Duncan RC, Zheng T, Michelotti G, Levens D. The far upstream element-binding proteins comprise an ancient family of single-strand DNA-binding transactivators. J Biol Chem. 1996 Dec 6;271(49):31679-87. PMID:8940189
- ↑ Markovtsov V, Nikolic JM, Goldman JA, Turck CW, Chou MY, Black DL. Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol Cell Biol. 2000 Oct;20(20):7463-79. PMID:11003644
- ↑ Diaz-Moreno I, Hollingworth D, Frenkiel TA, Kelly G, Martin S, Howell S, Garcia-Mayoral M, Gherzi R, Briata P, Ramos A. Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding. Nat Struct Mol Biol. 2009 Mar;16(3):238-46. Epub 2009 Feb 8. PMID:19198587 doi:10.1038/nsmb.1558
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