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| | ==Crystal structure of the BCL6 BTB domain in complex with F1324(10-13)== | | ==Crystal structure of the BCL6 BTB domain in complex with F1324(10-13)== |
| - | <StructureSection load='5h7h' size='340' side='right' caption='[[5h7h]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='5h7h' size='340' side='right'caption='[[5h7h]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5h7h]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H7H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H7H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5h7h]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_phage_T7 Escherichia phage T7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H7H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H7H FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5h7g|5h7g]]</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=5h7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h7h OCA], [https://pdbe.org/5h7h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h7h RCSB], [https://www.ebi.ac.uk/pdbsum/5h7h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h7h ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5h7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h7h OCA], [http://pdbe.org/5h7h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h7h RCSB], [http://www.ebi.ac.uk/pdbsum/5h7h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h7h ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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. | + | [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 == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5h7h" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5h7h" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ida, K]] | + | [[Category: Escherichia phage T7]] |
| - | [[Category: Lane, W]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Snell, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Sogabe, S]] | + | [[Category: Ida K]] |
| - | [[Category: Complex]] | + | [[Category: Lane W]] |
| - | [[Category: Inhibitor]] | + | [[Category: Snell G]] |
| - | [[Category: Transcription repressor]] | + | [[Category: Sogabe S]] |
| - | [[Category: Transcription-inhibitor complex]]
| + | |
| Structural highlights
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]
Publication Abstract from PubMed
B cell lymphoma 6 (BCL6) is a transcriptional repressor that interacts with its corepressors BcoR and SMRT. Since this protein-protein interaction (PPI) induces activation and differentiation of B lymphocytes, BCL6 has been an attractive drug target for potential autoimmune disease treatments. Here we report a novel BCL6 inhibitory peptide, F1324 (Ac-LWYTDIRMSWRVP-OH), which we discovered using phage display technology; we also discuss this peptide's structure-activity relationship (SAR). For BCL6(5-129) binding, KD and IC50 values of F1324 were 0.57 nM and 1 nM according to the results of an SPR analysis and cell-free ELISA assay, respectively. In contrast, BcoR(Arg498-514Pro) and SMRT(Leu1422-Arg1438) exhibited relatively weak micromole-order binding to BCL6. Furthermore, Fusion protein AcGFP-F1324 transiently expressed in HEK293T cells inhibited intracellular PPI in cell-based M2H assay. By examination of the truncation and fragmentation of F1324, the C-terminal sequence WRVP, which is similar to the BcoR(509-512) sequence WVVP, was identified as being critical for BCL6 binding. In addition, subsequent single-crystal X-ray diffraction analysis of F1324/BCL6(5-129) complex revealed that the high affinity of F1324 was caused by effective interaction of its side chains while its main chain structure was similar to that of BcoR(Arg498-514Pro). To our knowledge, F1324 is the strongest BCL6-binding peptide yet reported.
Discovery of high-affinity BCL6-binding peptide and its structure-activity relationship.,Sakamoto K, Sogabe S, Kamada Y, Sakai N, Asano K, Yoshimatsu M, Ida K, Imaeda Y, Sakamoto JI Biochem Biophys Res Commun. 2016 Nov 14. pii: S0006-291X(16)31916-7. doi:, 10.1016/j.bbrc.2016.11.060. PMID:27856253[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ Sakamoto K, Sogabe S, Kamada Y, Sakai N, Asano K, Yoshimatsu M, Ida K, Imaeda Y, Sakamoto JI. Discovery of high-affinity BCL6-binding peptide and its structure-activity relationship. Biochem Biophys Res Commun. 2016 Nov 14. pii: S0006-291X(16)31916-7. doi:, 10.1016/j.bbrc.2016.11.060. PMID:27856253 doi:http://dx.doi.org/10.1016/j.bbrc.2016.11.060
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