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| | ==Crystal structure of Isl1 LIM domains with Ldb1 LIM-interaction domain== | | ==Crystal structure of Isl1 LIM domains with Ldb1 LIM-interaction domain== |
| - | <StructureSection load='4jcj' size='340' side='right' caption='[[4jcj]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4jcj' size='340' side='right'caption='[[4jcj]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jcj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JCJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JCJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jcj]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JCJ 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">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ldb1, Nli ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4jcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jcj OCA], [http://pdbe.org/4jcj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jcj RCSB], [http://www.ebi.ac.uk/pdbsum/4jcj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jcj 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=4jcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jcj OCA], [https://pdbe.org/4jcj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jcj RCSB], [https://www.ebi.ac.uk/pdbsum/4jcj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jcj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ISL1_MOUSE ISL1_MOUSE]] Binds and regulates the promoters of the insulin, glucagon and somatostatin genes. Involved in the specificarion of motor neurons in cooperation with LHX3 and LDB1. | + | [https://www.uniprot.org/uniprot/ISL1_MOUSE ISL1_MOUSE] Binds and regulates the promoters of the insulin, glucagon and somatostatin genes. Involved in the specificarion of motor neurons in cooperation with LHX3 and LDB1.[https://www.uniprot.org/uniprot/LDB1_MOUSE LDB1_MOUSE] Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. May play a role in the development of motor neurons. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state.<ref>PMID:8918878</ref> <ref>PMID:8876198</ref> <ref>PMID:9192866</ref> <ref>PMID:9391090</ref> <ref>PMID:16815859</ref> <ref>PMID:9315627</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Gadd, M S]] | + | [[Category: Mus musculus]] |
| - | [[Category: Guss, J M]] | + | [[Category: Gadd MS]] |
| - | [[Category: Jacques, D A]] | + | [[Category: Guss JM]] |
| - | [[Category: Matthews, J M]] | + | [[Category: Jacques DA]] |
| - | [[Category: Nucleus]] | + | [[Category: Matthews JM]] |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Transcriptional complex]]
| + | |
| - | [[Category: Zinc binding]]
| + | |
| - | [[Category: Zinc finger]]
| + | |
| Structural highlights
Function
ISL1_MOUSE Binds and regulates the promoters of the insulin, glucagon and somatostatin genes. Involved in the specificarion of motor neurons in cooperation with LHX3 and LDB1.LDB1_MOUSE Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. May play a role in the development of motor neurons. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Islet 1 (Isl1) is a transcription factor of the LIM-homeodomain (LIM-HD) protein family and is essential for many developmental processes. LIM-HD proteins all contain two protein-interacting LIM domains, a DNA-binding homeodomain (HD), and a C-terminal region. In Isl1, the C-terminal region also contains the LIM homeobox 3 (Lhx3)-binding domain (LBD), which interacts with the LIM domains of Lhx3. The LIM domains of Isl1 have been implicated in inhibition of DNA binding potentially through an intramolecular interaction with or close to the HD. Here we investigate the LBD as a candidate intramolecular interaction domain. Competitive yeast-two hybrid experiments indicate that the LIM domains and LBD from Isl1 can interact with apparently low affinity, consistent with no detection of an intermolecular interaction in the same system. Nuclear magnetic resonance studies show that the interaction is specific, whereas substitution of the LBD with peptides of the same amino acid composition but different sequence is not specific. We solved the crystal structure of a similar but higher affinity complex between the LIM domains of Isl1 and the LIM interaction domain from the LIM-HD cofactor protein LIM domain-binding protein 1 (Ldb1) and used these coordinates to generate a homology model of the intramolecular interaction that indicates poorer complementarity for the weak intramolecular interaction. The intramolecular interaction in Isl1 may provide protection against aggregation, minimize unproductive DNA binding, and facilitate cofactor exchange within the cell.
A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions.,Gadd MS, Jacques DA, Nisevic I, Craig VJ, Kwan AH, Guss JM, Matthews JM J Biol Chem. 2013 Jul 26;288(30):21924-35. doi: 10.1074/jbc.M113.478586. Epub, 2013 Jun 9. PMID:23750000[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Agulnick AD, Taira M, Breen JJ, Tanaka T, Dawid IB, Westphal H. Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins. Nature. 1996 Nov 21;384(6606):270-2. PMID:8918878 doi:http://dx.doi.org/10.1038/384270a0
- ↑ Jurata LW, Kenny DA, Gill GN. Nuclear LIM interactor, a rhombotin and LIM homeodomain interacting protein, is expressed early in neuronal development. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11693-8. PMID:8876198
- ↑ Bach I, Carriere C, Ostendorff HP, Andersen B, Rosenfeld MG. A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins. Genes Dev. 1997 Jun 1;11(11):1370-80. PMID:9192866
- ↑ Visvader JE, Mao X, Fujiwara Y, Hahm K, Orkin SH. The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13707-12. PMID:9391090
- ↑ Tran YH, Xu Z, Kato A, Mistry AC, Goya Y, Taira M, Brandt SJ, Hirose S. Spliced isoforms of LIM-domain-binding protein (CLIM/NLI/Ldb) lacking the LIM-interaction domain. J Biochem. 2006 Jul;140(1):105-19. Epub 2006 Jun 30. PMID:16815859 doi:http://dx.doi.org/10.1093/jb/mvj134
- ↑ Jurata LW, Gill GN. Functional analysis of the nuclear LIM domain interactor NLI. Mol Cell Biol. 1997 Oct;17(10):5688-98. PMID:9315627
- ↑ Gadd MS, Jacques DA, Nisevic I, Craig VJ, Kwan AH, Guss JM, Matthews JM. A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions. J Biol Chem. 2013 Jul 26;288(30):21924-35. doi: 10.1074/jbc.M113.478586. Epub, 2013 Jun 9. PMID:23750000 doi:http://dx.doi.org/10.1074/jbc.M113.478586
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