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[[Image:1r2b.gif|left|200px]]<br /><applet load="1r2b" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1r2b, resolution 2.2&Aring;" />
'''Crystal structure of the BCL6 BTB domain complexed with a SMRT co-repressor peptide'''<br />


==Overview==
==Crystal structure of the BCL6 BTB domain complexed with a SMRT co-repressor peptide==
BCL6 encodes a transcription factor that represses genes necessary for the terminal differentiation of lymphocytes within germinal centers, and the misregulated expression of this factor is strongly implicated in several types of B cell lymphoma. The homodimeric BTB domain of BCL6 (also known as the POZ domain) is required for the repression activity of the protein and interacts directly with the SMRT and N-CoR corepressors that are found within large multiprotein histone deacetylase-containing complexes. We have identified a 17 residue fragment from SMRT that binds to the BCL6 BTB domain, and determined the crystal structure of the complex to 2.2 A. Two SMRT fragments bind symmetrically to the BCL6 BTB homodimer and, in combination with biochemical and in vivo data, the structure provides insight into the basis of transcriptional repression by this critical B cell lymphoma protein.
<StructureSection load='1r2b' size='340' side='right'caption='[[1r2b]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1r2b]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R2B 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]] 2.2&#8491;</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=1r2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r2b OCA], [https://pdbe.org/1r2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r2b RCSB], [https://www.ebi.ac.uk/pdbsum/1r2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r2b ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN] Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions.  Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1.  Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
== Function ==
[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN] Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.<ref>PMID:9649500</ref> <ref>PMID:18280243</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r2/1r2b_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1r2b ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Diabetes mellitus, neonatal, with congenital hypothyroidism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=610192 610192]], Lymphoma, B-cell OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109565 109565]]
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 
*[[Nuclear receptor corepressor|Nuclear receptor corepressor]]
==About this Structure==
== References ==
1R2B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R2B OCA].
<references/>
 
__TOC__
==Reference==
</StructureSection>
Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain., Ahmad KF, Melnick A, Lax S, Bouchard D, Liu J, Kiang CL, Mayer S, Takahashi S, Licht JD, Prive GG, Mol Cell. 2003 Dec;12(6):1551-64. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14690607 14690607]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Ahmad, K F.]]
[[Category: Ahmad KF]]
[[Category: Bouchard, D.]]
[[Category: Bouchard D]]
[[Category: Kiang, C L.]]
[[Category: Kiang CL]]
[[Category: Lax, S A.]]
[[Category: Lax SA]]
[[Category: Licht, J D.]]
[[Category: Licht JD]]
[[Category: Liu, J.]]
[[Category: Liu J]]
[[Category: Mayer, S.]]
[[Category: Mayer S]]
[[Category: Melnick, A.]]
[[Category: Melnick A]]
[[Category: Prive, G G.]]
[[Category: Prive GG]]
[[Category: b-cell lymphoma]]
[[Category: btb domain]]
[[Category: hdac complex]]
[[Category: transcriptional repression]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:46:14 2008''

Latest revision as of 11:19, 14 February 2024

Crystal structure of the BCL6 BTB domain complexed with a SMRT co-repressor peptideCrystal structure of the BCL6 BTB domain complexed with a SMRT co-repressor peptide

Structural highlights

1r2b is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

BCL6_HUMAN Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.

Function

BCL6_HUMAN Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.[1] [2]

Evolutionary Conservation

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

See Also

References

  1. ↑ Niu H, Ye BH, Dalla-Favera R. Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes Dev. 1998 Jul 1;12(13):1953-61. PMID:9649500
  2. ↑ Ghetu AF, Corcoran CM, Cerchietti L, Bardwell VJ, Melnick A, Prive GG. Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer. Mol Cell. 2008 Feb 15;29(3):384-91. PMID:18280243 doi:10.1016/j.molcel.2007.12.026

1r2b, resolution 2.20Å

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