[English] 日本語
Yorodumi
- PDB-7jn7: Human DPP9-CARD8 complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7jn7
TitleHuman DPP9-CARD8 complex
Components
  • Caspase recruitment domain-containing protein 8
  • Dipeptidyl peptidase 9
KeywordsIMMUNE SYSTEM / HYDROLASE / CARD8 / DPP9 / inflammasome / Val-boroPro (VbP) / talabostat / innate immunity
Function / homology
Function and homology information


CARD8 inflammasome complex assembly / CARD8 inflammasome complex / NACHT domain binding / Formation of apoptosome / cysteine-type endopeptidase activator activity / inhibition of cysteine-type endopeptidase activity / NLRP3 inflammasome complex / CARD domain binding / negative regulation of NLRP3 inflammasome complex assembly / negative regulation of lipopolysaccharide-mediated signaling pathway ...CARD8 inflammasome complex assembly / CARD8 inflammasome complex / NACHT domain binding / Formation of apoptosome / cysteine-type endopeptidase activator activity / inhibition of cysteine-type endopeptidase activity / NLRP3 inflammasome complex / CARD domain binding / negative regulation of NLRP3 inflammasome complex assembly / negative regulation of lipopolysaccharide-mediated signaling pathway / dipeptidyl-peptidase IV / self proteolysis / dipeptidyl-peptidase activity / negative regulation of programmed cell death / Regulation of the apoptosome activity / regulation of canonical NF-kappaB signal transduction / Hydrolases; Acting on peptide bonds (peptidases) / pattern recognition receptor activity / negative regulation of interleukin-1 beta production / negative regulation of NF-kappaB transcription factor activity / pyroptotic inflammatory response / : / cell leading edge / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of tumor necrosis factor-mediated signaling pathway / aminopeptidase activity / negative regulation of canonical NF-kappaB signal transduction / antiviral innate immune response / serine-type peptidase activity / positive regulation of interleukin-1 beta production / molecular condensate scaffold activity / peptidase activity / defense response to virus / regulation of apoptotic process / microtubule / protein homodimerization activity / protein-containing complex / proteolysis / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
FIIND domain / Function to find / FIIND domain profile. / Dipeptidyl peptidase 8 /9 ,N-terminal / Dipeptidyl peptidase 8 and 9 N-terminal / : / : / Dipeptidylpeptidase IV, N-terminal domain / Dipeptidyl peptidase IV (DPP IV) N-terminal region / CARD domain ...FIIND domain / Function to find / FIIND domain profile. / Dipeptidyl peptidase 8 /9 ,N-terminal / Dipeptidyl peptidase 8 and 9 N-terminal / : / : / Dipeptidylpeptidase IV, N-terminal domain / Dipeptidyl peptidase IV (DPP IV) N-terminal region / CARD domain / CARD caspase recruitment domain profile. / Caspase recruitment domain / Peptidase S9, prolyl oligopeptidase, catalytic domain / Prolyl oligopeptidase family / Death-like domain superfamily / Alpha/Beta hydrolase fold
Similarity search - Domain/homology
Chem-GK2 / Dipeptidyl peptidase 9 / Caspase recruitment domain-containing protein 8
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsSharif, H. / Hollingsworth, L.R.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 Al124491 United States
CitationJournal: Immunity / Year: 2021
Title: Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment.
Authors: Humayun Sharif / L Robert Hollingsworth / Andrew R Griswold / Jeffrey C Hsiao / Qinghui Wang / Daniel A Bachovchin / Hao Wu /
Abstract: CARD8 detects intracellular danger signals and forms a caspase-1 activating inflammasome. Like the related inflammasome sensor NLRP1, CARD8 autoprocesses into noncovalently associated N-terminal (NT) ...CARD8 detects intracellular danger signals and forms a caspase-1 activating inflammasome. Like the related inflammasome sensor NLRP1, CARD8 autoprocesses into noncovalently associated N-terminal (NT) and C-terminal (CT) fragments and binds the cellular dipeptidyl peptidases DPP8 and 9 (DPP8/9). Certain danger-associated signals, including the DPP8/9 inhibitor Val-boroPro (VbP) and HIV protease, induce proteasome-mediated NT degradation and thereby liberate the inflammasome-forming CT. Here, we report cryoelectron microscopy (cryo-EM) structures of CARD8 bound to DPP9, revealing a repressive ternary complex consisting of DPP9, full-length CARD8, and CARD8-CT. Unlike NLRP1-CT, CARD8-CT does not interact with the DPP8/9 active site and is not directly displaced by VbP. However, larger DPP8/9 active-site probes can directly weaken this complex in vitro, and VbP itself nevertheless appears to disrupt this complex, perhaps indirectly, in cells. Thus, DPP8/9 inhibitors can activate the CARD8 inflammasome by promoting CARD8 NT degradation and by weakening ternary complex stability.
History
DepositionAug 4, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 19, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 9, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jul 28, 2021Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first
Revision 1.3Oct 23, 2024Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / em_admin / pdbx_entry_details / pdbx_initial_refinement_model / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type / _em_admin.last_update / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-22402
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dipeptidyl peptidase 9
B: Caspase recruitment domain-containing protein 8
C: Caspase recruitment domain-containing protein 8
D: Dipeptidyl peptidase 9
hetero molecules


Theoretical massNumber of molelcules
Total (without water)325,3866
Polymers324,9584
Non-polymers4282
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area8220 Å2
ΔGint-35 kcal/mol
Surface area79950 Å2

-
Components

#1: Protein Dipeptidyl peptidase 9 / DP9 / Dipeptidyl peptidase IV-related protein 2 / DPRP-2 / Dipeptidyl peptidase IX / DPP IX / ...DP9 / Dipeptidyl peptidase IV-related protein 2 / DPRP-2 / Dipeptidyl peptidase IX / DPP IX / Dipeptidyl peptidase-like protein 9 / DPLP9


Mass: 101761.984 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DPP9, DPRP2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q86TI2, dipeptidyl-peptidase IV
#2: Protein Caspase recruitment domain-containing protein 8 / Apoptotic protein NDPP1 / CARD-inhibitor of NF-kappa-B-activating ligand / CARDINAL / DACAR / Tumor ...Apoptotic protein NDPP1 / CARD-inhibitor of NF-kappa-B-activating ligand / CARDINAL / DACAR / Tumor up-regulated CARD-containing antagonist of CASP9 / TUCAN / CARD8


Mass: 60716.875 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CARD8, KIAA0955, NDPP1 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q9Y2G2
#3: Chemical ChemComp-GK2 / [(2~{R})-1-[(2~{R})-2-azanyl-3-methyl-butanoyl]pyrrolidin-2-yl]boronic acid


Mass: 214.070 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C9H19BN2O3 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: DPP9-CARD8 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human) / Cell: HEK293 / Plasmid: pcDNA3.1
Buffer solutionpH: 7.5 / Details: 25 mM HEPES, pH 7.5, 150 mM NaCl, 1 mM TCEP
SpecimenConc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 278 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: OTHER / Calibrated magnification: 10500 X / Nominal defocus max: 2200 nm / Nominal defocus min: -800 nm / Cs: 2.7 mm
Specimen holderSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recording

Imaging-ID: 1 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 4

IDAverage exposure time (sec.)Electron dose (e/Å2)Num. of real imagesDetails
12.2258.53306stage tilt 0 degrees
22.2564.992488stage tilt 37 degrees

-
Processing

SoftwareName: PHENIX / Version: 1.18.2_3874: / Classification: refinement
EM software
IDNameVersionCategory
1crYOLO1.5particle selection
2SerialEM3.7image acquisition
4CTFFIND9.03CTF correction
7PHENIX1.18.1model fitting
9PHENIX1.18.1model refinement
10RELION3.1initial Euler assignment
11RELION3.1final Euler assignment
12RELION3.1classification
13RELION3.13D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1404573 / Details: no tilt dataset
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 205538 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT
Atomic model buildingProtocol: OTHER
Atomic model buildingPDB-ID: 6EOQ

6eoq


Pdb chain-ID: A / Accession code: 6EOQ / Source name: PDB / Type: experimental model
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00917315
ELECTRON MICROSCOPYf_angle_d1.32123530
ELECTRON MICROSCOPYf_dihedral_angle_d8.9582273
ELECTRON MICROSCOPYf_chiral_restr0.0772479
ELECTRON MICROSCOPYf_plane_restr0.0113056

+
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