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6gk2

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Current revision

Helical reconstruction of BCL10 CARD and MALT1 DEATH DOMAIN complex

6gk2, resolution 4.90Å

Structural highlights

6gk2 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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. [MALT1_HUMAN] Note=A chromosomal aberration involving MALT1 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with BIRC2. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.

Function

[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.^[1] [MALT1_HUMAN] Enhances BCL10-induced activation of NF-kappa-B. Involved in nuclear export of BCL10. Binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity. Has ubiquitin ligase activity. MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion.^[2] ^[3] ^[4]

Publication Abstract from PubMed

The CARD11-BCL10-MALT1 (CBM) complex triggers the adaptive immune response in lymphocytes and lymphoma cells. CARD11/CARMA1 acts as a molecular seed inducing BCL10 filaments, but the integration of MALT1 and the assembly of a functional CBM complex has remained elusive. Using cryo-EM we solved the helical structure of the BCL10-MALT1 filament. The structural model of the filament core solved at 4.9 A resolution identified the interface between the N-terminal MALT1 DD and the BCL10 caspase recruitment domain. The C-terminal MALT1 Ig and paracaspase domains protrude from this core to orchestrate binding of mediators and substrates at the filament periphery. Mutagenesis studies support the importance of the identified BCL10-MALT1 interface for CBM complex assembly, MALT1 protease activation and NF-kappaB signaling in Jurkat and primary CD4 T-cells. Collectively, we present a model for the assembly and architecture of the CBM signaling complex and how it functions as a signaling hub in T-lymphocytes.

Molecular architecture and regulation of BCL10-MALT1 filaments.,Schlauderer F, Seeholzer T, Desfosses A, Gehring T, Strauss M, Hopfner KP, Gutsche I, Krappmann D, Lammens K Nat Commun. 2018 Oct 2;9(1):4041. doi: 10.1038/s41467-018-06573-8. PMID:30279415^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rebeaud F, Hailfinger S, Posevitz-Fejfar A, Tapernoux M, Moser R, Rueda D, Gaide O, Guzzardi M, Iancu EM, Rufer N, Fasel N, Thome M. The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat Immunol. 2008 Mar;9(3):272-81. doi: 10.1038/ni1568. Epub 2008 Feb 10. PMID:18264101 doi:10.1038/ni1568
↑ Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G. Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem. 2001 Jun 1;276(22):19012-9. Epub 2001 Mar 21. PMID:11262391 doi:10.1074/jbc.M009984200
↑ Zhou H, Wertz I, O'Rourke K, Ultsch M, Seshagiri S, Eby M, Xiao W, Dixit VM. Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature. 2004 Jan 8;427(6970):167-71. Epub 2003 Dec 24. PMID:14695475 doi:10.1038/nature02273
↑ Rebeaud F, Hailfinger S, Posevitz-Fejfar A, Tapernoux M, Moser R, Rueda D, Gaide O, Guzzardi M, Iancu EM, Rufer N, Fasel N, Thome M. The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat Immunol. 2008 Mar;9(3):272-81. doi: 10.1038/ni1568. Epub 2008 Feb 10. PMID:18264101 doi:10.1038/ni1568
↑ Schlauderer F, Seeholzer T, Desfosses A, Gehring T, Strauss M, Hopfner KP, Gutsche I, Krappmann D, Lammens K. Molecular architecture and regulation of BCL10-MALT1 filaments. Nat Commun. 2018 Oct 2;9(1):4041. doi: 10.1038/s41467-018-06573-8. PMID:30279415 doi:http://dx.doi.org/10.1038/s41467-018-06573-8

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6gk2"

@@ Line 1: / Line 1: @@
 ==Helical reconstruction of BCL10 CARD and MALT1 DEATH DOMAIN complex==
-<StructureSection load='6gk2' size='340' side='right' caption='[[6gk2]], [[Resolution|resolution]] 4.90&Aring;' scene=''>
+<SX load='6gk2' size='340' side='right' viewer='molstar' caption='[[6gk2]], [[Resolution|resolution]] 4.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6gk2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GK2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6gk2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GK2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6GK2 FirstGlance]. <br>
-</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=6gk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gk2 OCA], [http://pdbe.org/6gk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gk2 RCSB], [http://www.ebi.ac.uk/pdbsum/6gk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gk2 ProSAT]</span></td></tr>
+</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=6gk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gk2 OCA], [http://pdbe.org/6gk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gk2 RCSB], [http://www.ebi.ac.uk/pdbsum/6gk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gk2 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6gk2" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 == References ==
 <references/>
 __TOC__
-</StructureSection>
+</SX>
+[[Category: Large Structures]]
 [[Category: Desfosses, A]]
 [[Category: Gutsche, I]]

6gk2

From Proteopedia

Current revision

Helical reconstruction of BCL10 CARD and MALT1 DEATH DOMAIN complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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