View source for 4jcj


==Crystal structure of Isl1 LIM domains with Ldb1 LIM-interaction domain==
<StructureSection load='4jcj' size='340' side='right'caption='[[4jcj]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</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=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>
== Function ==
[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;">
== 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<ref>PMID:23750000</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4jcj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Gadd MS]]
[[Category: Guss JM]]
[[Category: Jacques DA]]
[[Category: Matthews JM]]