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| | ==NMR Solution Structure of a ldb1-LID:Lhx3-LIM complex== | | ==NMR Solution Structure of a ldb1-LID:Lhx3-LIM complex== |
| - | <StructureSection load='2jtn' size='340' side='right'caption='[[2jtn]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2jtn' size='340' side='right'caption='[[2jtn]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2jtn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JTN FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2jtn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JTN FirstGlance]. <br> |
| - | </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> | + | </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">Ldb1, Nli, Lhx3, Lim-3, Lim3, Plim ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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'>[https://proteopedia.org/fgij/fg.htm?mol=2jtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jtn OCA], [https://pdbe.org/2jtn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jtn RCSB], [https://www.ebi.ac.uk/pdbsum/2jtn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jtn 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=2jtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jtn OCA], [https://pdbe.org/2jtn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jtn RCSB], [https://www.ebi.ac.uk/pdbsum/2jtn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jtn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [https://www.uniprot.org/uniprot/LHX3_MOUSE LHX3_MOUSE] Required for the establishment of the specialized cells of the pituitary gland and the nervous system (By similarity). Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1. Acts as a transcriptional activator. Binds to and activates the promoter of the alpha-glycoprotein gene, and synergistically enhances transcription from the prolactin promoter in cooperation with Pou1f1/Pit-1.<ref>PMID:10593900</ref> <ref>PMID:12150931</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Lee, C]] | + | [[Category: Lee C]] |
| - | [[Category: Mackay, J P]] | + | [[Category: Mackay JP]] |
| - | [[Category: Matthews, J M]] | + | [[Category: Matthews JM]] |
| - | [[Category: Nancarrow, A L]] | + | [[Category: Nancarrow AL]] |
| - | [[Category: Protein binding-transcription complex]]
| + | |
| Structural highlights
Function
LHX3_MOUSE Required for the establishment of the specialized cells of the pituitary gland and the nervous system (By similarity). Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1. Acts as a transcriptional activator. Binds to and activates the promoter of the alpha-glycoprotein gene, and synergistically enhances transcription from the prolactin promoter in cooperation with Pou1f1/Pit-1.[1] [2]
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
LIM-homeodomain (LIM-HD) transcription factors form a combinatorial 'LIM code' that contributes to the specification of cell types. In the ventral spinal cord, the binary LIM homeobox protein 3 (Lhx3)/LIM domain-binding protein 1 (Ldb1) complex specifies the formation of V2 interneurons. The additional expression of islet-1 (Isl1) in adjacent cells instead specifies the formation of motor neurons through assembly of a ternary complex in which Isl1 contacts both Lhx3 and Ldb1, displacing Lhx3 as the binding partner of Ldb1. However, little is known about how this molecular switch occurs. Here, we have identified the 30-residue Lhx3-binding domain on Isl1 (Isl1(LBD)). Although the LIM interaction domain of Ldb1 (Ldb1(LID)) and Isl1(LBD) share low levels of sequence homology, X-ray and NMR structures reveal that they bind Lhx3 in an identical manner, that is, Isl1(LBD) mimics Ldb1(LID). These data provide a structural basis for the formation of cell type-specific protein-protein interactions in which unstructured linear motifs with diverse sequences compete to bind protein partners. The resulting alternate protein complexes can target different genes to regulate key biological events.
Implementing the LIM code: the structural basis for cell type-specific assembly of LIM-homeodomain complexes.,Bhati M, Lee C, Nancarrow AL, Lee M, Craig VJ, Bach I, Guss JM, Mackay JP, Matthews JM EMBO J. 2008 Jul 23;27(14):2018-29. Epub 2008 Jun 26. PMID:18583962[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Glenn DJ, Maurer RA. MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression. J Biol Chem. 1999 Dec 17;274(51):36159-67. PMID:10593900
- ↑ Thaler JP, Lee SK, Jurata LW, Gill GN, Pfaff SL. LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions. Cell. 2002 Jul 26;110(2):237-49. PMID:12150931
- ↑ Bhati M, Lee C, Nancarrow AL, Lee M, Craig VJ, Bach I, Guss JM, Mackay JP, Matthews JM. Implementing the LIM code: the structural basis for cell type-specific assembly of LIM-homeodomain complexes. EMBO J. 2008 Jul 23;27(14):2018-29. Epub 2008 Jun 26. PMID:18583962 doi:10.1038/emboj.2008.123
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