[English] 日本語
Yorodumi
- PDB-8btb: Hexameric human IgG3 Fc complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8btb
TitleHexameric human IgG3 Fc complex
Components(FLJ00385 protein (Fragment)) x 2
KeywordsIMMUNE SYSTEM / IgG3 / antibody / Fc hexamer
Function / homology
Function and homology information


: / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / subtomogram averaging / cryo EM / Resolution: 14 Å
AuthorsAbendstein, L. / Sharp, T.H.
Funding supportEuropean Union, Netherlands, 3items
OrganizationGrant numberCountry
European Research Council (ERC)759517European Union
Netherlands Organisation for Scientific Research (NWO)OCENW.KLEIN.291 Netherlands
Netherlands Organisation for Scientific Research (NWO)VI.Vidi.193.014 Netherlands
CitationJournal: Nat Commun / Year: 2023
Title: Complement is activated by elevated IgG3 hexameric platforms and deposits C4b onto distinct antibody domains.
Authors: Leoni Abendstein / Douwe J Dijkstra / Rayman T N Tjokrodirijo / Peter A van Veelen / Leendert A Trouw / Paul J Hensbergen / Thomas H Sharp /
Abstract: IgG3 is unique among the IgG subclasses due to its extended hinge, allotypic diversity and enhanced effector functions, including highly efficient pathogen neutralisation and complement activation. ...IgG3 is unique among the IgG subclasses due to its extended hinge, allotypic diversity and enhanced effector functions, including highly efficient pathogen neutralisation and complement activation. It is also underrepresented as an immunotherapeutic candidate, partly due to a lack of structural information. Here, we use cryoEM to solve structures of antigen-bound IgG3 alone and in complex with complement components. These structures reveal a propensity for IgG3-Fab clustering, which is possible due to the IgG3-specific flexible upper hinge region and may maximise pathogen neutralisation by forming high-density antibody arrays. IgG3 forms elevated hexameric Fc platforms that extend above the protein corona to maximise binding to receptors and the complement C1 complex, which here adopts a unique protease conformation that may precede C1 activation. Mass spectrometry reveals that C1 deposits C4b directly onto specific IgG3 residues proximal to the Fab domains. Structural analysis shows this to be caused by the height of the C1-IgG3 complex. Together, these data provide structural insights into the role of the unique IgG3 extended hinge, which will aid the development and design of upcoming immunotherapeutics based on IgG3.
History
DepositionNov 28, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 21, 2023Provider: repository / Type: Initial release
Revision 1.1Jul 19, 2023Group: Data collection / Database references / Category: citation / citation_author / pdbx_validate_planes
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _pdbx_validate_planes.type
Revision 1.2Nov 20, 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 / pdbx_validate_planes
Item: _em_admin.last_update / _pdbx_validate_planes.type

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: FLJ00385 protein (Fragment)
B: FLJ00385 protein (Fragment)
K: FLJ00385 protein (Fragment)
L: FLJ00385 protein (Fragment)
I: FLJ00385 protein (Fragment)
J: FLJ00385 protein (Fragment)
G: FLJ00385 protein (Fragment)
H: FLJ00385 protein (Fragment)
E: FLJ00385 protein (Fragment)
F: FLJ00385 protein (Fragment)
C: FLJ00385 protein (Fragment)
D: FLJ00385 protein (Fragment)


Theoretical massNumber of molelcules
Total (without water)285,31112
Polymers285,31112
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein
FLJ00385 protein (Fragment)


Mass: 23768.957 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FLJ00385 / Cell (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q8NF17
#2: Protein
FLJ00385 protein (Fragment)


Mass: 23782.943 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FLJ00385 / Cell (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q8NF17
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: subtomogram averaging

-
Sample preparation

ComponentName: Fc domain of human IgG3 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human) / Cell: Expi293F
Buffer solutionpH: 7.4 / Details: PBS
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TECNAI ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 6000 nm / Nominal defocus min: 3000 nm
Image recordingElectron dose: 1.5 e/Å2 / Avg electron dose per subtomogram: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM software
IDNameCategory
1EMAN2volume selection
4IMODCTF correction
7UCSF ChimeraXmodel fitting
10Dynamofinal Euler assignment
11Dynamoclassification
12Dynamo3D reconstruction
13PHENIXmodel refinement
CTF correctionType: PHASE FLIPPING ONLY
SymmetryPoint symmetry: C6 (6 fold cyclic)
3D reconstructionResolution: 14 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 571 / Symmetry type: POINT
EM volume selectionNum. of tomograms: 60 / Num. of volumes extracted: 1193
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00620286
ELECTRON MICROSCOPYf_angle_d1.21527648
ELECTRON MICROSCOPYf_dihedral_angle_d9.4852652
ELECTRON MICROSCOPYf_chiral_restr0.0653084
ELECTRON MICROSCOPYf_plane_restr0.023564

+
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