8czd

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
==Cryo-EM structure of BCL10 R58Q filament==
==Cryo-EM structure of BCL10 R58Q filament==
-
<StructureSection load='8czd' size='340' side='right'caption='[[8czd]]' scene=''>
+
<StructureSection load='8czd' size='340' side='right'caption='[[8czd]], [[Resolution|resolution]] 4.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CZD FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[8czd]] is a 20 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CZD FirstGlance]. <br>
</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=8czd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8czd OCA], [https://pdbe.org/8czd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8czd RCSB], [https://www.ebi.ac.uk/pdbsum/8czd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8czd ProSAT]</span></td></tr>
</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=8czd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8czd OCA], [https://pdbe.org/8czd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8czd RCSB], [https://www.ebi.ac.uk/pdbsum/8czd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8czd ProSAT]</span></td></tr>
</table>
</table>
 +
== Disease ==
 +
[[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 ==
 +
[[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 ==
 +
ABC-DLBCLs have unfavorable outcomes and chronic activation of CBM signal amplification complexes that form due to polymerization of BCL10 subunits, which is affected by recurrent somatic mutations in ABC-DLBCLs. Herein, we show that BCL10 mutants fall into at least two functionally distinct classes: missense mutations of the BCL10 CARD domain and truncation of its C-terminal tail. Truncating mutation abrogated a novel motif through which MALT1 inhibits BCL10 polymerization, trapping MALT1 in its activated filament-bound state. CARD missense mutation enhanced BCL10 filament formation; forming glutamine network structures that stabilize BCL10 filaments. Mutant forms of BCL10 were less dependent on upstream CARD11 activation and thus manifested resistance to BTK inhibitors, whereas BCL10 truncating but not CARD mutants were hypersensitive to MALT1 inhibitors. Therefore, BCL10 mutations are potential biomarkers for BTK inhibitor resistance in ABC-DLBCL and further precision can be achieved by selecting therapy based on specific biochemical effects of distinct mutation classes.
 +
 +
BCL10 mutations define distinct dependencies guiding precision therapy for DLBCL.,Xia M, David L, Teater M, Gutierrez J, Wang X, Meydan C, Lytle A, Slack GW, Scott DW, Morin RD, Onder O, Elenitoba-Johnson KSJ, Zamponi N, Cerchietti L, Lu T, Philippar U, Fontan L, Wu H, Melnick AM Cancer Discov. 2022 Jun 3. pii: 699375. doi: 10.1158/2159-8290.CD-21-1566. PMID:35658124<ref>PMID:35658124</ref>
 +
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 8czd" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: David L]]
+
[[Category: David, L]]
-
[[Category: Wu H]]
+
[[Category: Wu, H]]
 +
[[Category: Cbm complex]]
 +
[[Category: Filament]]
 +
[[Category: Immune system]]

Revision as of 07:36, 29 June 2022

Cryo-EM structure of BCL10 R58Q filament

PDB ID 8czd

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools