[English] 日本語
Yorodumi
- PDB-8czo: Cryo-EM structure of BCL10 CARD - MALT1 DD filament -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8czo
TitleCryo-EM structure of BCL10 CARD - MALT1 DD filament
Components
  • B-cell lymphoma/leukemia 10
  • Mucosa-associated lymphoid tissue lymphoma translocation protein 1
KeywordsIMMUNE SYSTEM / filament / CBM complex
Function / homology
Function and homology information


positive regulation of lymphotoxin A production / polkadots / B-1 B cell differentiation / positive regulation of T-helper 17 cell differentiation / CBM complex / regulation of T cell receptor signaling pathway / protein kinase B binding / antifungal innate immune response / response to fungus / positive regulation of mast cell cytokine production ...positive regulation of lymphotoxin A production / polkadots / B-1 B cell differentiation / positive regulation of T-helper 17 cell differentiation / CBM complex / regulation of T cell receptor signaling pathway / protein kinase B binding / antifungal innate immune response / response to fungus / positive regulation of mast cell cytokine production / CARD domain binding / T cell apoptotic process / negative regulation of mature B cell apoptotic process / B cell apoptotic process / CLEC7A/inflammasome pathway / programmed cell death / nuclear export / positive regulation of extrinsic apoptotic signaling pathway / non-canonical NF-kappaB signal transduction / response to food / toll-like receptor signaling pathway / positive regulation of T cell receptor signaling pathway / small molecule binding / B cell activation / immunoglobulin mediated immune response / immunological synapse / general transcription initiation factor binding / endopeptidase activator activity / NF-kappaB binding / cellular defense response / positive regulation of phosphorylation / T cell proliferation / cytoplasmic microtubule / signaling adaptor activity / positive regulation of interleukin-2 production / lipopolysaccharide-mediated signaling pathway / proteolysis involved in protein catabolic process / positive regulation of interleukin-1 beta production / positive regulation of protein ubiquitination / positive regulation of interleukin-8 production / neural tube closure / apoptotic signaling pathway / Activation of NF-kappaB in B cells / defense response / positive regulation of T cell cytokine production / protein homooligomerization / positive regulation of interleukin-6 production / CLEC7A (Dectin-1) signaling / positive regulation of T cell activation / FCERI mediated NF-kB activation / fibrillar center / cellular response to mechanical stimulus / positive regulation of NF-kappaB transcription factor activity / ubiquitin-protein transferase activity / Downstream TCR signaling / E3 ubiquitin ligases ubiquitinate target proteins / peptidase activity / T cell receptor signaling pathway / cellular response to lipopolysaccharide / protease binding / protein-macromolecule adaptor activity / regulation of apoptotic process / endopeptidase activity / adaptive immune response / positive regulation of canonical NF-kappaB signal transduction / transcription coactivator activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / lysosome / positive regulation of apoptotic process / membrane raft / innate immune response / cysteine-type endopeptidase activity / ubiquitin protein ligase binding / protein-containing complex binding / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / perinuclear region of cytoplasm / protein-containing complex / proteolysis / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
B-cell lymphoma/leukemia 10/E10 / BCL10, CARD domain / Mucosa-associated lymphoid tissue lymphoma translocation protein 1 / MALT1, death domain / MALT1 immunoglobulin-like domain / : / MALT1 Ig-like domain / CARD domain / CARD caspase recruitment domain profile. / Caspase recruitment domain ...B-cell lymphoma/leukemia 10/E10 / BCL10, CARD domain / Mucosa-associated lymphoid tissue lymphoma translocation protein 1 / MALT1, death domain / MALT1 immunoglobulin-like domain / : / MALT1 Ig-like domain / CARD domain / CARD caspase recruitment domain profile. / Caspase recruitment domain / Immunoglobulin domain / Peptidase C14, p20 domain / Caspase family p20 domain profile. / : / Caspase domain / Caspase-like domain superfamily / Immunoglobulin domain / Death-like domain superfamily / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
B-cell lymphoma/leukemia 10 / Mucosa-associated lymphoid tissue lymphoma translocation protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 4.3 Å
AuthorsDavid, L. / Wu, H.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cancer Discov / Year: 2022
Title: BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy for DLBCL.
Authors: Min Xia / Liron David / Matt Teater / Johana Gutierrez / Xiang Wang / Cem Meydan / Andrew Lytle / Graham W Slack / David W Scott / Ryan D Morin / Ozlem Onder / Kojo S J Elenitoba-Johnson / ...Authors: Min Xia / Liron David / Matt Teater / Johana Gutierrez / Xiang Wang / Cem Meydan / Andrew Lytle / Graham W Slack / David W Scott / Ryan D Morin / Ozlem Onder / Kojo S J Elenitoba-Johnson / Nahuel Zamponi / Leandro Cerchietti / Tianbao Lu / Ulrike Philippar / Lorena Fontan / Hao Wu / Ari M Melnick /
Abstract: Activated B cell-like diffuse large B-cell lymphomas (ABC-DLBCL) have unfavorable outcomes and chronic activation of CARD11-BCL10-MALT1 (CBM) signal amplification complexes that form due to ...Activated B cell-like diffuse large B-cell lymphomas (ABC-DLBCL) have unfavorable outcomes and chronic activation of CARD11-BCL10-MALT1 (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 mutations abrogated a motif through which MALT1 inhibits BCL10 polymerization, trapping MALT1 in its activated filament-bound state. CARD missense mutations 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.
SIGNIFICANCE: ABC-DLBCLs feature frequent mutations of signaling mediators that converge on the CBM complex. We use structure-function approaches to reveal that BCL10 mutations fall into two distinct ...SIGNIFICANCE: ABC-DLBCLs feature frequent mutations of signaling mediators that converge on the CBM complex. We use structure-function approaches to reveal that BCL10 mutations fall into two distinct biochemical classes. Both classes confer resistance to BTK inhibitors, whereas BCL10 truncations confer hyperresponsiveness to MALT1 inhibitors, providing a road map for precision therapies in ABC-DLBCLs. See related commentary by Phelan and Oellerich, p. 1844. This article is highlighted in the In This Issue feature, p. 1825.
History
DepositionMay 25, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 22, 2022Provider: repository / Type: Initial release
Revision 1.1Jun 29, 2022Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Aug 17, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.3Oct 23, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
a: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
b: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
c: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
d: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
e: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
f: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
g: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
h: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
i: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
j: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
k: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
l: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
m: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
n: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
o: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
p: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
q: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
r: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
s: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
t: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
u: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
v: Mucosa-associated lymphoid tissue lymphoma translocation protein 1
A: B-cell lymphoma/leukemia 10
B: B-cell lymphoma/leukemia 10
C: B-cell lymphoma/leukemia 10
D: B-cell lymphoma/leukemia 10
E: B-cell lymphoma/leukemia 10
F: B-cell lymphoma/leukemia 10
G: B-cell lymphoma/leukemia 10
H: B-cell lymphoma/leukemia 10
I: B-cell lymphoma/leukemia 10
J: B-cell lymphoma/leukemia 10
K: B-cell lymphoma/leukemia 10
L: B-cell lymphoma/leukemia 10
M: B-cell lymphoma/leukemia 10
N: B-cell lymphoma/leukemia 10
O: B-cell lymphoma/leukemia 10
P: B-cell lymphoma/leukemia 10
Q: B-cell lymphoma/leukemia 10
R: B-cell lymphoma/leukemia 10
S: B-cell lymphoma/leukemia 10
T: B-cell lymphoma/leukemia 10
U: B-cell lymphoma/leukemia 10
V: B-cell lymphoma/leukemia 10


Theoretical massNumber of molelcules
Total (without water)511,05944
Polymers511,05944
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein ...
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 / MALT lymphoma-associated translocation / Paracaspase


Mass: 10615.389 Da / Num. of mol.: 22
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MALT1, MLT / Production host: Escherichia phage EcSzw-2 (virus)
References: UniProt: Q9UDY8, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases
#2: Protein ...
B-cell lymphoma/leukemia 10 / B-cell CLL/lymphoma 10 / Bcl-10 / CARD-containing molecule enhancing NF-kappa-B / CARD-like ...B-cell CLL/lymphoma 10 / Bcl-10 / CARD-containing molecule enhancing NF-kappa-B / CARD-like apoptotic protein / hCLAP / CED-3/ICH-1 prodomain homologous E10-like regulator / CIPER / Cellular homolog of vCARMEN / cCARMEN / Cellular-E10 / c-E10 / Mammalian CARD-containing adapter molecule E10 / mE10


Mass: 12614.566 Da / Num. of mol.: 22
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BCL10, CIPER, CLAP / Production host: Escherichia phage EcSzw-2 (virus) / References: UniProt: O95999
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: FILAMENT / 3D reconstruction method: helical reconstruction

-
Sample preparation

ComponentName: filament / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia phage EcSzw-2 (virus)
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
125 mMtrizma baseTris1
2150 mMSodium ChlorideNaCl1
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 %

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 47000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / C2 aperture diameter: 2.7 µm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 55 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 700

-
Processing

SoftwareName: PHENIX / Version: 1.18_3845: / Classification: refinement
EM softwareName: RELION / Version: 3.1 / Category: 3D reconstruction
CTF correctionType: NONE
Helical symmertyAngular rotation/subunit: -100.8 ° / Axial rise/subunit: 5 Å / Axial symmetry: C1
3D reconstructionResolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 23000 / Symmetry type: HELICAL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00434804
ELECTRON MICROSCOPYf_angle_d0.71246618
ELECTRON MICROSCOPYf_dihedral_angle_d8.114642
ELECTRON MICROSCOPYf_chiral_restr0.0445478
ELECTRON MICROSCOPYf_plane_restr0.0055962

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more