|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Solution structure of Tandem zinc finger domain 12 in Muscleblind-like protein 2== | | ==Solution structure of Tandem zinc finger domain 12 in Muscleblind-like protein 2== |
| - | <StructureSection load='2rpp' size='340' side='right' caption='[[2rpp]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2rpp' size='340' side='right'caption='[[2rpp]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2rpp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RPP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RPP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2rpp]] 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=2RPP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RPP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MBNL2, MBLL, MBLL39, MLP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2rpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rpp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rpp RCSB], [http://www.ebi.ac.uk/pdbsum/2rpp PDBsum], [http://www.topsan.org/Proteins/RSGI/2rpp 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=2rpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rpp OCA], [https://pdbe.org/2rpp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rpp RCSB], [https://www.ebi.ac.uk/pdbsum/2rpp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rpp ProSAT], [https://www.topsan.org/Proteins/RSGI/2rpp TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MBNL2_HUMAN MBNL2_HUMAN]] Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. RNA-binding protein that binds to 5'ACACCC-3' core sequence, termed zipcode, within the 3'UTR of ITGA3. Binds to CUG triplet repeat expansion in myotonic dystrophy muscle cells by sequestering the target RNAs. Seems to regulate expression and localization of ITGA3 by transporting it from the nucleus to cytoplasm at adhesion plaques. May play a role in myotonic dystrophy pathophysiology (DM).<ref>PMID:16273094</ref> <ref>PMID:15257297</ref> <ref>PMID:16946708</ref> | + | [https://www.uniprot.org/uniprot/MBNL2_HUMAN MBNL2_HUMAN] Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. RNA-binding protein that binds to 5'ACACCC-3' core sequence, termed zipcode, within the 3'UTR of ITGA3. Binds to CUG triplet repeat expansion in myotonic dystrophy muscle cells by sequestering the target RNAs. Seems to regulate expression and localization of ITGA3 by transporting it from the nucleus to cytoplasm at adhesion plaques. May play a role in myotonic dystrophy pathophysiology (DM).<ref>PMID:16273094</ref> <ref>PMID:15257297</ref> <ref>PMID:16946708</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rp/2rpp_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rp/2rpp_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </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/chain_selection.php?pdb_ID=2ata 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=2rpp ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| Line 27: |
Line 28: |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| - | | + | <div class="pdbe-citations 2rpp" style="background-color:#fffaf0;"></div> |
| - | ==See Also== | + | |
| - | *[[Zinc Fingers|Zinc Fingers]]
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 35: |
Line 34: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Abe, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Dang, W]] | + | [[Category: Abe C]] |
| - | [[Category: Inoue, M]] | + | [[Category: Dang W]] |
| - | [[Category: Kigawa, T]] | + | [[Category: Inoue M]] |
| - | [[Category: Muto, Y]] | + | [[Category: Kigawa T]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Muto Y]] |
| - | [[Category: Shirouzu, M]] | + | [[Category: Shirouzu M]] |
| - | [[Category: Terada, T]] | + | [[Category: Terada T]] |
| - | [[Category: Tsuda, K]] | + | [[Category: Tsuda K]] |
| - | [[Category: Yokoyama, S]] | + | [[Category: Yokoyama S]] |
| - | [[Category: C3h]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: National project on protein structural and functional analyse]]
| + | |
| - | [[Category: Nppsfa]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Rna-binding]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Zinc finger domain]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
MBNL2_HUMAN Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. RNA-binding protein that binds to 5'ACACCC-3' core sequence, termed zipcode, within the 3'UTR of ITGA3. Binds to CUG triplet repeat expansion in myotonic dystrophy muscle cells by sequestering the target RNAs. Seems to regulate expression and localization of ITGA3 by transporting it from the nucleus to cytoplasm at adhesion plaques. May play a role in myotonic dystrophy pathophysiology (DM).[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 muscleblind-like (MBNL) proteins 1, 2, and 3, which contain four CCCH zinc finger motifs (ZF1-4), are involved in the differentiation of muscle inclusion by controlling the splicing patterns of several pre-mRNAs. Especially, MBNL1 plays a crucial role in myotonic dystrophy. The CCCH zinc finger is a sequence motif found in many RNA binding proteins and is suggested to play an important role in the recognition of RNA molecules. Here, we solved the solution structures of both tandem zinc finger (TZF) motifs, TZF12 (comprising ZF1 and ZF2) and TZF34 (ZF3 and ZF4), in MBNL2 from Homo sapiens. In TZF12 of MBNL2, ZF1 and ZF2 adopt a similar fold, as reported previously for the CCCH-type zinc fingers in the TIS11d protein. The linker between ZF1 and ZF2 in MBNL2 forms an antiparallel beta-sheet with the N-terminal extension of ZF1. Furthermore, ZF1 and ZF2 in MBNL2 interact with each other through hydrophobic interactions. Consequently, TZF12 forms a single, compact global fold, where ZF1 and ZF2 are approximately symmetrical about the C2 axis. The structure of the second tandem zinc finger (TZF34) in MBNL2 is similar to that of TZF12. This novel three-dimensional structure of the TZF domains in MBNL2 provides a basis for functional studies of the CCCH-type zinc finger motifs in the MBNL protein family.
Solution structure of the RNA binding domain in the human muscleblind-like protein 2.,He F, Dang W, Abe C, Tsuda K, Inoue M, Watanabe S, Kobayashi N, Kigawa T, Matsuda T, Yabuki T, Aoki M, Seki E, Harada T, Tomabechi Y, Terada T, Shirouzu M, Tanaka A, Guntert P, Muto Y, Yokoyama S Protein Sci. 2009 Jan;18(1):80-91. PMID:19177353[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Adereth Y, Dammai V, Kose N, Li R, Hsu T. RNA-dependent integrin alpha3 protein localization regulated by the Muscleblind-like protein MLP1. Nat Cell Biol. 2005 Dec;7(12):1240-7. Epub 2005 Nov 6. PMID:16273094 doi:http://dx.doi.org/ncb1335
- ↑ Ho TH, Charlet-B N, Poulos MG, Singh G, Swanson MS, Cooper TA. Muscleblind proteins regulate alternative splicing. EMBO J. 2004 Aug 4;23(15):3103-12. Epub 2004 Jul 15. PMID:15257297 doi:10.1038/sj.emboj.7600300
- ↑ Paul S, Dansithong W, Kim D, Rossi J, Webster NJ, Comai L, Reddy S. Interaction of muscleblind, CUG-BP1 and hnRNP H proteins in DM1-associated aberrant IR splicing. EMBO J. 2006 Sep 20;25(18):4271-83. Epub 2006 Aug 31. PMID:16946708 doi:10.1038/sj.emboj.7601296
- ↑ He F, Dang W, Abe C, Tsuda K, Inoue M, Watanabe S, Kobayashi N, Kigawa T, Matsuda T, Yabuki T, Aoki M, Seki E, Harada T, Tomabechi Y, Terada T, Shirouzu M, Tanaka A, Guntert P, Muto Y, Yokoyama S. Solution structure of the RNA binding domain in the human muscleblind-like protein 2. Protein Sci. 2009 Jan;18(1):80-91. PMID:19177353 doi:10.1002/pro.17
|
