[English] 日本語
Yorodumi
- PDB-8rnu: CryoEM structure of recombinant human Bri2 BRICHOS oligomers -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8rnu
TitleCryoEM structure of recombinant human Bri2 BRICHOS oligomers
ComponentsIntegral membrane protein 2B
KeywordsCHAPERONE / anti-amyloid / dementia / Bri2
Function / homology
Function and homology information


negative regulation of amyloid precursor protein biosynthetic process / Golgi-associated vesicle membrane / organelle membrane / nervous system development / amyloid-beta binding / endosome membrane / Amyloid fiber formation / Golgi membrane / intracellular membrane-bounded organelle / Golgi apparatus ...negative regulation of amyloid precursor protein biosynthetic process / Golgi-associated vesicle membrane / organelle membrane / nervous system development / amyloid-beta binding / endosome membrane / Amyloid fiber formation / Golgi membrane / intracellular membrane-bounded organelle / Golgi apparatus / extracellular space / extracellular exosome / extracellular region / ATP binding / membrane / plasma membrane
Similarity search - Function
Integral membrane protein 2 / BRICHOS / BRICHOS domain / BRICHOS domain / BRICHOS domain profile.
Similarity search - Domain/homology
Integral membrane protein 2B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsChen, G. / Johansson, J. / Hebert, H.
Funding support Sweden, 1items
OrganizationGrant numberCountry
Swedish Research Council Sweden
CitationJournal: Protein Sci / Year: 2024
Title: Molecular basis for different substrate-binding sites and chaperone functions of the BRICHOS domain.
Authors: Gefei Chen / Yu Wang / Zihan Zheng / Wangshu Jiang / Axel Leppert / Xueying Zhong / Anna Belorusova / Gregg Siegal / Caroline Jegerschöld / Philip J B Koeck / Axel Abelein / Hans Hebert / ...Authors: Gefei Chen / Yu Wang / Zihan Zheng / Wangshu Jiang / Axel Leppert / Xueying Zhong / Anna Belorusova / Gregg Siegal / Caroline Jegerschöld / Philip J B Koeck / Axel Abelein / Hans Hebert / Stefan D Knight / Jan Johansson /
Abstract: Proteins can misfold into fibrillar or amorphous aggregates and molecular chaperones act as crucial guardians against these undesirable processes. The BRICHOS chaperone domain, found in several ...Proteins can misfold into fibrillar or amorphous aggregates and molecular chaperones act as crucial guardians against these undesirable processes. The BRICHOS chaperone domain, found in several otherwise unrelated proproteins that contain amyloidogenic regions, effectively inhibits amyloid formation and toxicity but can in some cases also prevent non-fibrillar, amorphous protein aggregation. Here, we elucidate the molecular basis behind the multifaceted chaperone activities of the BRICHOS domain from the Bri2 proprotein. High-confidence AlphaFold2 and RoseTTAFold predictions suggest that the intramolecular amyloidogenic region (Bri23) is part of the hydrophobic core of the proprotein, where it occupies the proposed amyloid binding site, explaining the markedly reduced ability of the proprotein to prevent an exogenous amyloidogenic peptide from aggregating. However, the BRICHOS-Bri23 complex maintains its ability to form large polydisperse oligomers that prevent amorphous protein aggregation. A cryo-EM-derived model of the Bri2 BRICHOS oligomer is compatible with surface-exposed hydrophobic motifs that get exposed and come together during oligomerization, explaining its effects against amorphous aggregation. These findings provide a molecular basis for the BRICHOS chaperone domain function, where distinct surfaces are employed against different forms of protein aggregation.
History
DepositionJan 11, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 19, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Integral membrane protein 2B
K: Integral membrane protein 2B
E: Integral membrane protein 2B
I: Integral membrane protein 2B
C: Integral membrane protein 2B
G: Integral membrane protein 2B
B: Integral membrane protein 2B
H: Integral membrane protein 2B
D: Integral membrane protein 2B
J: Integral membrane protein 2B
F: Integral membrane protein 2B
L: Integral membrane protein 2B


Theoretical massNumber of molelcules
Total (without water)167,40012
Polymers167,40012
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein
Integral membrane protein 2B / Immature BRI2 / imBRI2 / Protein E25B / Transmembrane protein BRI / Bri


Mass: 13949.985 Da / Num. of mol.: 12
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ITM2B, BRI, BRI2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9Y287

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Recombinant human Bri2 BRICHOS oligomers / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightValue: 0.205 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 8
SpecimenConc.: 0.08 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/2
VitrificationInstrument: FEI VITROBOT MARK II / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 288 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 defocus max: 3500 nm / Nominal defocus min: 1400 nm
Image recordingAverage exposure time: 8 sec. / Electron dose: 44.8 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k)
Image scansMovie frames/image: 40

-
Processing

EM software
IDNameCategory
1RELIONparticle selection
7RELIONmodel fitting
13PHENIXmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 589803
SymmetryPoint symmetry: D3 (2x3 fold dihedral)
3D reconstructionResolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 146177 / Symmetry type: POINT
Atomic model buildingB value: 420 / Protocol: FLEXIBLE FIT / Space: REAL
Atomic model buildingSource name: AlphaFold / Type: in silico model
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.02611064
ELECTRON MICROSCOPYf_angle_d1.10615024
ELECTRON MICROSCOPYf_dihedral_angle_d6.4961404
ELECTRON MICROSCOPYf_chiral_restr0.0481764
ELECTRON MICROSCOPYf_plane_restr0.0091920

+
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://pdbjlvh1.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