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[[Image:3brd.jpg|left|200px]]


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==CSL (Lag-1) bound to DNA with Lin-12 RAM peptide, P212121==
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<StructureSection load='3brd' size='340' side='right'caption='[[3brd]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3brd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BRD FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.21&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
{{STRUCTURE_3brd|  PDB=3brd  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3brd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3brd OCA], [https://pdbe.org/3brd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3brd RCSB], [https://www.ebi.ac.uk/pdbsum/3brd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3brd ProSAT]</span></td></tr>
 
</table>
'''CSL (Lag-1) bound to DNA with Lin-12 RAM peptide, P212121'''
== Function ==
 
[https://www.uniprot.org/uniprot/LAG1_CAEEL LAG1_CAEEL] Transcriptional regulator that plays a central role in lin-12/Notch and glp-1/Notch signaling pathways, involved in cell-cell communication that regulate a broad spectrum of cell-fate determinations (PubMed:8625826). Binds directly to the 5'-[A/G]TGGGAA-3' DNA consensus sequence, which is present in the regulatory region of several genes (PubMed:8625826, PubMed:18706403, PubMed:23615264, PubMed:15297877, PubMed:32196486, PubMed:21737278). Acts as a transcriptional repressor when it is not associated with Notch proteins (By similarity). When in a complex with a Notch intracellular domain (NICD) product of lin-12/Notch or glp-1/Notch, and transcription regulator lag-3, it may act as a transcriptional activator that activates transcription of target genes(PubMed:18381292, PubMed:10830967, PubMed:32196486, PubMed:9003776). Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively (By similarity). Autonomously required in the germline for the stem cell fate, acting in the glp-1-dependent transcriptional activation of genes, including lst-1 and sygl-1 (PubMed:32196486). Involved in cell-fate specification during reproductive system development, by positively autoregulating its own expression, in response to lin-12/Notch signaling (PubMed:23615264, PubMed:32839181). Plays a role in Notch-dependent induction of left-right asymmetry in interneurons and motoneurons (PubMed:21737278). May repress expression of hlh-6, in a lin-12/Notch-independent manner (PubMed:18706403).[UniProtKB:P28159]<ref>PMID:10830967</ref> <ref>PMID:15297877</ref> <ref>PMID:18381292</ref> <ref>PMID:18706403</ref> <ref>PMID:21737278</ref> <ref>PMID:23615264</ref> <ref>PMID:32196486</ref> <ref>PMID:32839181</ref> <ref>PMID:8625826</ref>
 
== Evolutionary Conservation ==
==Overview==
[[Image:Consurf_key_small.gif|200px|right]]
The Notch pathway is a conserved cell-to-cell signaling mechanism, in which extracellular signals are transduced into transcriptional outputs through the nuclear effector CSL. CSL is converted from a repressor to an activator through the formation of the CSL-NotchIC-Mastermind ternary complex. The RAM domain of NotchIC avidly interacts with CSL; however, its role in assembly of the CSL-NotchIC-Mastermind ternary complex is not understood. Here we provide a comprehensive thermodynamic, structural, and biochemical analysis of the RAM-CSL interaction for components from both mouse and worm. Our binding data shows that RAM and CSL form a high affinity complex in the presence or absence of DNA. Our structural studies reveal a striking distal conformational change in CSL upon RAM binding, which creates a docking site for Mastermind to bind to the complex. Finally, we show that the addition of a RAM peptide in trans facilitates formation of the CSL-NotchIC-Mastermind ternary complex in vitro.
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==About this Structure==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/br/3brd_consurf.spt"</scriptWhenChecked>
3BRD is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BRD OCA].  
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    <text>to colour the structure by Evolutionary Conservation</text>
==Reference==
  </jmolCheckbox>
RAM induced allostery facilitates assembly of a notch pathway active transcription complex., Friedmann DR, Wilson JJ, Kovall RA, J Biol Chem. 2008 Apr 1;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18381292 18381292]
</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=3brd ConSurf].
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caenorhabditis elegans]]
[[Category: Caenorhabditis elegans]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Kovall, R A.]]
[[Category: Kovall RA]]
[[Category: Wilson, J J.]]
[[Category: Wilson JJ]]
[[Category: Ank repeat]]
[[Category: Developmental protein]]
[[Category: Differentiation]]
[[Category: Dna binding protein/dna complex]]
[[Category: Dna-binding]]
[[Category: Egf-like domain]]
[[Category: Glycoprotein]]
[[Category: Membrane]]
[[Category: Notch]]
[[Category: Protein-dna complex]]
[[Category: Signaling]]
[[Category: Transcription]]
[[Category: Transmembrane]]
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