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| <SX load='6bze' size='340' side='right' viewer='molstar' caption='[[6bze]], [[Resolution|resolution]] 4.00Å' scene=''> | | <SX load='6bze' size='340' side='right' viewer='molstar' caption='[[6bze]], [[Resolution|resolution]] 4.00Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6bze]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BZE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BZE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bze]] is a 8 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=6BZE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BZE FirstGlance]. <br> |
- | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCL10, CIPER, CLAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4Å</td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6bze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bze OCA], [http://pdbe.org/6bze PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bze RCSB], [http://www.ebi.ac.uk/pdbsum/6bze PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bze ProSAT]</span></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=6bze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bze OCA], [https://pdbe.org/6bze PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bze RCSB], [https://www.ebi.ac.uk/pdbsum/6bze PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bze ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
- | [[http://www.uniprot.org/uniprot/BCL10_HUMAN BCL10_HUMAN]] A chromosomal aberration involving BCL10 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(1;14)(p22;q32). Although the BCL10/IgH translocation leaves the coding region of BCL10 intact, frequent BCL10 mutations could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. Defects in BCL10 are involved in various types of cancer. The gene represented in this entry may be involved in disease pathogenesis. | + | [https://www.uniprot.org/uniprot/BCL10_HUMAN BCL10_HUMAN] A chromosomal aberration involving BCL10 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(1;14)(p22;q32). Although the BCL10/IgH translocation leaves the coding region of BCL10 intact, frequent BCL10 mutations could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. Defects in BCL10 are involved in various types of cancer. The gene represented in this entry may be involved in disease pathogenesis. |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/BCL10_HUMAN BCL10_HUMAN]] Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK. May be an adapter protein between upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP complex. Is a substrate for MALT1.<ref>PMID:18264101</ref> | + | [https://www.uniprot.org/uniprot/BCL10_HUMAN BCL10_HUMAN] Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK. May be an adapter protein between upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP complex. Is a substrate for MALT1.<ref>PMID:18264101</ref> |
- | <div style="background-color:#fffaf0;">
| + | |
- | == Publication Abstract from PubMed ==
| + | |
- | The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-kappaB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates B cell lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase with structural similarity to caspases, which recruits TNF receptor-associated factor 6 (TRAF6) for K63-linked polyubiquitination. Here we present cryo-electron microscopy (cryo-EM) structure of the BCL10 CARD filament at 4.0-A resolution. The structure redefines CARD-CARD interactions compared with the previous EM structure determined from a negatively stained sample. Surprisingly, time-lapse confocal imaging shows that BCL10 polymerizes in a unidirectional manner. CARMA1, the BCL10 nucleator, serves as a hub for formation of star-shaped filamentous networks of BCL10 and significantly decreases the lag period of BCL10 polymerization. Cooperative MALT1 interaction with BCL10 filaments observed under EM suggests immediate dimerization of MALT1 in the BCL10 filamentous scaffold. In addition, TRAF6 cooperatively decorates CBM filaments to form higher-order assemblies, likely resulting in all-or-none activation of the downstream pathway. Collectively, these data reveal biophysical mechanisms in the assembly of the CARMA1-BCL10-MALT1-TRAF6 complex for signal transduction.
| + | |
- | | + | |
- | Assembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome.,David L, Li Y, Ma J, Garner E, Zhang X, Wu H Proc Natl Acad Sci U S A. 2018 Jan 30. pii: 1721967115. doi:, 10.1073/pnas.1721967115. PMID:29382759<ref>PMID:29382759</ref>
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- | | + | |
- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
- | </div>
| + | |
- | <div class="pdbe-citations 6bze" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
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| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
- | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: David, L]] | + | [[Category: David L]] |
- | [[Category: Garner, E]] | + | [[Category: Garner E]] |
- | [[Category: Li, Y]] | + | [[Category: Li Y]] |
- | [[Category: Ma, J]] | + | [[Category: Ma J]] |
- | [[Category: Wu, H]] | + | [[Category: Wu H]] |
- | [[Category: Zhang, X]] | + | [[Category: Zhang X]] |
- | [[Category: Card]]
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- | [[Category: Filament]]
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- | [[Category: Helical reconstruction]]
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- | [[Category: Signaling protein]]
| + | |
- | [[Category: Signalosome]]
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