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[[Image:1ttu.gif|left|200px]]


{{Structure
==Crystal Structure of CSL bound to DNA==
|PDB= 1ttu |SIZE=350|CAPTION= <scene name='initialview01'>1ttu</scene>, resolution 2.85&Aring;
<StructureSection load='1ttu' size='340' side='right'caption='[[1ttu]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>
<table><tr><td colspan='2'>[[1ttu]] is a 3 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=1TTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TTU FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85&#8491;</td></tr>
|GENE= lag-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 Caenorhabditis elegans])
<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>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ttu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ttu OCA], [https://pdbe.org/1ttu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ttu RCSB], [https://www.ebi.ac.uk/pdbsum/1ttu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ttu ProSAT]</span></td></tr>
 
</table>
'''Crystal Structure of CSL bound to DNA'''
== 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]]
Notch signaling is a conserved pathway of communication between neighboring cells that results in cell fate specification, and CSL is the universal transcriptional effector of Notch signaling. The Notch intracellular domain translocates to the nucleus after proteolytic release upon Notch extracellular engagement, and there it displaces corepressors from DNA-bound CSL and recruits activators of Notch target genes. Here we report the 2.85 A crystal structure of CSL with a target DNA. CSL comprises three structurally integrated domains: its amino (NTD)- and carboxy (CTD)-terminal domains are strikingly similar to those of Rel transcription factors, but a surprising beta-trefoil domain (BTD) is inserted between them. CSL-bound DNA is recognized specifically by conserved residues from NTD and BTD. A hydrophobic pocket on BTD is identified as the likely site of Notch interaction with CSL, which has functional implications for the mechanism of Notch signaling.
Check<jmol>
 
  <jmolCheckbox>
==About this Structure==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tt/1ttu_consurf.spt"</scriptWhenChecked>
1TTU is a [[Single protein]] structure of sequence 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=1TTU OCA].  
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 
    <text>to colour the structure by Evolutionary Conservation</text>
==Reference==
  </jmolCheckbox>
Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA., Kovall RA, Hendrickson WA, EMBO J. 2004 Sep 1;23(17):3441-51. Epub 2004 Aug 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15297877 15297877]
</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=1ttu ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caenorhabditis elegans]]
[[Category: Caenorhabditis elegans]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Hendrickson, W A.]]
[[Category: Hendrickson WA]]
[[Category: Kovall, R A.]]
[[Category: Kovall RA]]
[[Category: EDO]]
[[Category: beta-trefoil domain]]
[[Category: csl]]
[[Category: notch signaling]]
[[Category: protein-dna complex]]
[[Category: rel homology region]]
[[Category: transcription factor]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:23:04 2008''

Latest revision as of 11:42, 14 February 2024

Crystal Structure of CSL bound to DNACrystal Structure of CSL bound to DNA

Structural highlights

1ttu is a 3 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.85Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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][1] [2] [3] [4] [5] [6] [7] [8] [9]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Petcherski AG, Kimble J. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature. 2000 May 18;405(6784):364-8. PMID:10830967 doi:10.1038/35012645
  2. ↑ Kovall RA, Hendrickson WA. Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA. EMBO J. 2004 Sep 1;23(17):3441-51. Epub 2004 Aug 5. PMID:15297877 doi:10.1038/sj.emboj.7600349
  3. ↑ Friedmann DR, Wilson JJ, Kovall RA. RAM-induced allostery facilitates assembly of a notch pathway active transcription complex. J Biol Chem. 2008 May 23;283(21):14781-91. Epub 2008 Apr 1. PMID:18381292 doi:http://dx.doi.org/10.1074/jbc.M709501200
  4. ↑ Ghai V, Gaudet J. The CSL transcription factor LAG-1 directly represses hlh-6 expression in C. elegans. Dev Biol. 2008 Oct 15;322(2):334-44. PMID:18706403 doi:10.1016/j.ydbio.2008.07.018
  5. ↑ Bertrand V, Bisso P, Poole RJ, Hobert O. Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons. Curr Biol. 2011 Jul 26;21(14):1225-31. PMID:21737278 doi:10.1016/j.cub.2011.06.016
  6. ↑ Choi VN, Park SK, Hwang BJ. Clustered LAG-1 binding sites in lag-1/CSL are involved in regulating lag-1 expression during lin-12/Notch-dependent cell-fate specification. BMB Rep. 2013 Apr;46(4):219-24. PMID:23615264 doi:10.5483/bmbrep.2013.46.4.269
  7. ↑ Chen J, Mohammad A, Pazdernik N, Huang H, Bowman B, Tycksen E, Schedl T. GLP-1 Notch-LAG-1 CSL control of the germline stem cell fate is mediated by transcriptional targets lst-1 and sygl-1. PLoS Genet. 2020 Mar 20;16(3):e1008650. PMID:32196486 doi:10.1371/journal.pgen.1008650
  8. ↑ Luo KL, Underwood RS, Greenwald I. Positive autoregulation of lag-1 in response to LIN-12 activation in cell fate decisions during C. elegans reproductive system development. Development. 2020 Sep 28;147(18):dev193482. PMID:32839181 doi:10.1242/dev.193482
  9. ↑ Christensen S, Kodoyianni V, Bosenberg M, Friedman L, Kimble J. lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H). Development. 1996 May;122(5):1373-83. PMID:8625826 doi:10.1242/dev.122.5.1373

1ttu, resolution 2.85Å

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