[English] 日本語
Yorodumi
- PDB-8pvy: Cryo-EM structure of the human BRISC dimer complex bound to compo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8pvy
TitleCryo-EM structure of the human BRISC dimer complex bound to compound FX-171-C
Components
  • (BRISC and BRCA1-A complex member ...) x 2
  • BRISC complex subunit Abraxas 2
  • Lys-63-specific deubiquitinase BRCC36
KeywordsSIGNALING PROTEIN / BRISC / BRCC36 / deubiquitylase / inhibitor / complex
Function / homology
Function and homology information


peroxisome targeting sequence binding / BRISC complex / BRCA1-A complex / attachment of spindle microtubules to kinetochore / nuclear ubiquitin ligase complex / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / regulation of DNA damage checkpoint / mitotic G2/M transition checkpoint / tumor necrosis factor receptor binding / metal-dependent deubiquitinase activity ...peroxisome targeting sequence binding / BRISC complex / BRCA1-A complex / attachment of spindle microtubules to kinetochore / nuclear ubiquitin ligase complex / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / regulation of DNA damage checkpoint / mitotic G2/M transition checkpoint / tumor necrosis factor receptor binding / metal-dependent deubiquitinase activity / protein K63-linked deubiquitination / K63-linked deubiquitinase activity / response to ionizing radiation / hematopoietic stem cell proliferation / DNA repair-dependent chromatin remodeling / positive regulation of NLRP3 inflammasome complex assembly / mitotic G2 DNA damage checkpoint signaling / polyubiquitin modification-dependent protein binding / protein deubiquitination / mitotic spindle assembly / response to X-ray / ubiquitin ligase complex / regulation of DNA repair / enzyme regulator activity / positive regulation of DNA repair / response to ischemia / cellular response to ionizing radiation / chromosome segregation / Nonhomologous End-Joining (NHEJ) / G2/M DNA damage checkpoint / Metalloprotease DUBs / spindle pole / metallopeptidase activity / double-strand break repair / mitotic cell cycle / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / Processing of DNA double-strand break ends / microtubule binding / microtubule / cysteine-type deubiquitinase activity / nuclear body / ciliary basal body / cell division / apoptotic process / DNA damage response / negative regulation of apoptotic process / signal transduction / proteolysis / nucleoplasm / metal ion binding / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
BRISC and BRCA1-A complex member 1 / FAM175 family, BRISC complex, Abro1 subunit / BRCA1-A complex subunit BRE / Brain and reproductive organ-expressed protein (BRE) / Brcc36 isopeptidase / BRCC36, C-terminal helical domain / BRCC36 C-terminal helical domain / FAM175 family / BRCA1-A complex subunit Abraxas 1 MPN domain / : ...BRISC and BRCA1-A complex member 1 / FAM175 family, BRISC complex, Abro1 subunit / BRCA1-A complex subunit BRE / Brain and reproductive organ-expressed protein (BRE) / Brcc36 isopeptidase / BRCC36, C-terminal helical domain / BRCC36 C-terminal helical domain / FAM175 family / BRCA1-A complex subunit Abraxas 1 MPN domain / : / JAB1/Mov34/MPN/PAD-1 ubiquitin protease / JAB/MPN domain / JAB1/MPN/MOV34 metalloenzyme domain / MPN domain / MPN domain profile. / von Willebrand factor A-like domain superfamily
Similarity search - Domain/homology
: / Lys-63-specific deubiquitinase BRCC36 / BRISC complex subunit Abraxas 2 / BRISC and BRCA1-A complex member 1 / BRISC and BRCA1-A complex member 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.02 Å
AuthorsChandler, F. / Zeqiraj, E.
Funding support United Kingdom, 2items
OrganizationGrant numberCountry
Wellcome Trust219997/Z/19/Z United Kingdom
Wellcome Trust United Kingdom
CitationJournal: To be published
Title: First-in-class DUB Molecular Glues and Inhibitors of Inflammation
Authors: Chandler, F. / Reddy, P. / Bhutda, S. / Ross, R. / Walden, M. / Walker, K. / Cassel, J. / Prakesch, M. / Datti, A. / Campbell, L. / Foglizzo, M. / Bell, L. / Ault, J. / Al-awar, R. / ...Authors: Chandler, F. / Reddy, P. / Bhutda, S. / Ross, R. / Walden, M. / Walker, K. / Cassel, J. / Prakesch, M. / Datti, A. / Campbell, L. / Foglizzo, M. / Bell, L. / Ault, J. / Al-awar, R. / Calabrese, A. / Sicheri, F. / Del Galdo, F. / Salvino, J. / Greenberg, R. / Zeqiraj, E.
History
DepositionJul 18, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 12, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Lys-63-specific deubiquitinase BRCC36
B: BRISC complex subunit Abraxas 2
C: Lys-63-specific deubiquitinase BRCC36
D: BRISC complex subunit Abraxas 2
E: BRISC and BRCA1-A complex member 2
F: BRISC and BRCA1-A complex member 2
G: Lys-63-specific deubiquitinase BRCC36
H: BRISC complex subunit Abraxas 2
I: Lys-63-specific deubiquitinase BRCC36
J: BRISC complex subunit Abraxas 2
K: BRISC and BRCA1-A complex member 2
L: BRISC and BRCA1-A complex member 2
M: BRISC and BRCA1-A complex member 1
N: BRISC and BRCA1-A complex member 1
O: BRISC and BRCA1-A complex member 1
P: BRISC and BRCA1-A complex member 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)560,96322
Polymers559,59516
Non-polymers1,3686
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable, mass spectrometry, native mass spectrometry indicated a 654 kDa complex, assay for oligomerization, mass photometry identified a 652 kDa complex
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

-
Protein , 2 types, 8 molecules ACGIBDHJ

#1: Protein
Lys-63-specific deubiquitinase BRCC36 / BRCA1-A complex subunit BRCC36 / BRCA1/BRCA2-containing complex subunit 3 / BRCA1/BRCA2-containing ...BRCA1-A complex subunit BRCC36 / BRCA1/BRCA2-containing complex subunit 3 / BRCA1/BRCA2-containing complex subunit 36 / BRISC complex subunit BRCC36


Mass: 35703.492 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRCC3, BRCC36, C6.1A, CXorf53 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P46736, Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases
#2: Protein
BRISC complex subunit Abraxas 2 / Abraxas brother protein 1 / Protein FAM175B


Mass: 31033.945 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ABRAXAS2, ABRO1, FAM175B, KIAA0157 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q15018

-
BRISC and BRCA1-A complex member ... , 2 types, 8 molecules EFKLMNOP

#3: Protein
BRISC and BRCA1-A complex member 2 / BRCA1-A complex subunit BRE / BRCA1/BRCA2-containing complex subunit 45 / Brain and reproductive ...BRCA1-A complex subunit BRE / BRCA1/BRCA2-containing complex subunit 45 / Brain and reproductive organ-expressed protein


Mass: 43721.602 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BABAM2, BRCC45, BRE / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9NXR7
#4: Protein
BRISC and BRCA1-A complex member 1 / Mediator of RAP80 interactions and targeting subunit of 40 kDa / New component of the BRCA1-A complex


Mass: 29439.723 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BABAM1, C19orf62, MERIT40, NBA1, HSPC142 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9NWV8

-
Non-polymers , 2 types, 6 molecules

#5: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn
#6: Chemical ChemComp-G1V / N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-1-[2,6-bis(chloranyl)phenyl]carbonyl-4-[[2,6-bis(chloranyl)phenyl]carbonylamino]pyrazole-3-carboxamide / N-(3-azabicyclo[3.1.0]hexan-6-yl)-4-(2,6-dichlorobenzamido)-1-(2,6-dichlorobenzoyl)-1H-pyrazole-3-carboxamide


Mass: 553.225 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H17Cl4N5O3 / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: BRISC dimer in complex with inhibitor FX-171-C / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT
Molecular weightValue: 0.654 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5 / Details: 25 mM HEPES pH 7.5, 150 mM NaCl, 1 mM TCEP
Buffer component
IDConc.NameFormulaBuffer-ID
125 mM4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidHEPES1
2150 mMsodium chlorideNaCl1
31 mMtris(2-carboxyethyl)phosphineTCEP1
SpecimenConc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: BRISCdNdC at 0.7 mg/mL (5 uM) was mixed with FX-171-C at 400 uM.
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K

-
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: 165000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1600 nm
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingAverage exposure time: 3.43 sec. / Electron dose: 34.97 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 16750
EM imaging opticsEnergyfilter name: TFS Selectris X / Energyfilter slit width: 10 eV

-
Processing

EM software
IDNameVersionCategory
1crYOLO1.6.1particle selection
2EPU3.2.0image acquisition
4CTFFINDCTF correction
9RELION3.1.1initial Euler assignment
10RELION3.1.1final Euler assignment
11RELION3.1.1classification
12RELION3.1.13D reconstruction
13PHENIXmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 2458785
3D reconstructionResolution: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 632988 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT / Space: REAL

+
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