[English] 日本語
Yorodumi
- PDB-7jic: Structure of human CD19-CD81 co-receptor complex bound to coltuxi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7jic
TitleStructure of human CD19-CD81 co-receptor complex bound to coltuximab Fab fragment
Components
  • B-lymphocyte antigen CD19
  • CD81 antigen
  • Coltuximab Heavy Chain
  • Coltuximab Light Chain
KeywordsIMMUNE SYSTEM / tetraspanin / Fab / complex
Function / homology
Function and homology information


regulation of B cell activation / positive regulation of adaptive immune memory response / antigen receptor-mediated signaling pathway / positive regulation of protein catabolic process in the vacuole / macrophage fusion / CD4-positive, alpha-beta T cell costimulation / positive regulation of B cell receptor signaling pathway / osteoclast fusion / B-1 B cell differentiation / myoblast fusion involved in skeletal muscle regeneration ...regulation of B cell activation / positive regulation of adaptive immune memory response / antigen receptor-mediated signaling pathway / positive regulation of protein catabolic process in the vacuole / macrophage fusion / CD4-positive, alpha-beta T cell costimulation / positive regulation of B cell receptor signaling pathway / osteoclast fusion / B-1 B cell differentiation / myoblast fusion involved in skeletal muscle regeneration / regulation of B cell receptor signaling pathway / positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / positive regulation of inflammatory response to antigenic stimulus / regulation of macrophage migration / immunological synapse formation / transferrin receptor binding / tetraspanin-enriched microdomain / positive regulation of protein exit from endoplasmic reticulum / protein localization to lysosome / positive regulation of T-helper 2 cell cytokine production / B cell proliferation involved in immune response / humoral immune response mediated by circulating immunoglobulin / MHC class II protein binding / positive regulation of CD4-positive, alpha-beta T cell proliferation / cholesterol binding / positive regulation of T cell receptor signaling pathway / immunoglobulin mediated immune response / cellular response to low-density lipoprotein particle stimulus / immunological synapse / positive regulation of receptor clustering / positive regulation of B cell proliferation / basal plasma membrane / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / positive regulation of release of sequestered calcium ion into cytosol / Regulation of Complement cascade / protein localization to plasma membrane / B cell receptor signaling pathway / regulation of protein stability / receptor internalization / integrin binding / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Constitutive Signaling by Aberrant PI3K in Cancer / MHC class II protein complex binding / PIP3 activates AKT signaling / virus receptor activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / basolateral plasma membrane / vesicle / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of MAPK cascade / membrane raft / external side of plasma membrane / focal adhesion / positive regulation of transcription by RNA polymerase II / protein-containing complex / extracellular exosome / membrane / plasma membrane / cytosol
Similarity search - Function
B-lymphocyte antigen CD19 / Tetraspanin, conserved site / Transmembrane 4 family signature. / Tetraspanin, animals / Tetraspanin, EC2 domain superfamily / Tetraspanin/Peripherin / Tetraspanin family / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. ...B-lymphocyte antigen CD19 / Tetraspanin, conserved site / Transmembrane 4 family signature. / Tetraspanin, animals / Tetraspanin, EC2 domain superfamily / Tetraspanin/Peripherin / Tetraspanin family / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
B-lymphocyte antigen CD19 / CD81 antigen
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsSusa, K.J. / Rawson, S. / Kruse, A.C. / Blacklow, S.C.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL 147459 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R35 CA220340 United States
National Institutes of Health/Office of the DirectorDP5 OD021345 United States
CitationJournal: Science / Year: 2021
Title: Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81.
Authors: Katherine J Susa / Shaun Rawson / Andrew C Kruse / Stephen C Blacklow /
Abstract: Signaling through the CD19-CD81 co-receptor complex, in combination with the B cell receptor, is a critical determinant of B cell development and activation. It is unknown how CD81 engages CD19 to ...Signaling through the CD19-CD81 co-receptor complex, in combination with the B cell receptor, is a critical determinant of B cell development and activation. It is unknown how CD81 engages CD19 to enable co-receptor function. Here, we report a 3.8-angstrom structure of the CD19-CD81 complex bound to a therapeutic antigen-binding fragment, determined by cryo-electron microscopy (cryo-EM). The structure includes both the extracellular domains and the transmembrane helices of the complex, revealing a contact interface between the ectodomains that drives complex formation. Upon binding to CD19, CD81 opens its ectodomain to expose a hydrophobic CD19-binding surface and reorganizes its transmembrane helices to occlude a cholesterol binding pocket present in the apoprotein. Our data reveal the structural basis for CD19-CD81 complex assembly, providing a foundation for rational design of therapies for B cell dysfunction.
History
DepositionJul 23, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 20, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 30, 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

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-22344
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: B-lymphocyte antigen CD19
B: CD81 antigen
H: Coltuximab Heavy Chain
L: Coltuximab Light Chain


Theoretical massNumber of molelcules
Total (without water)110,5174
Polymers110,5174
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein B-lymphocyte antigen CD19 / B-lymphocyte surface antigen B4 / Differentiation antigen CD19 / T-cell surface antigen Leu-12


Mass: 36031.578 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CD19 / Plasmid: pcDNA3.1 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: P15391
#2: Protein CD81 antigen / 26 kDa cell surface protein TAPA-1 / Target of the antiproliferative antibody 1 / Tetraspanin-28 / Tspan-28


Mass: 26444.758 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CD81, TAPA1, TSPAN28 / Plasmid: pcDNA3.1 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: P60033
#3: Antibody Coltuximab Heavy Chain


Mass: 24828.639 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Plasmid: pFUSE / Cell line (production host): Expi293F / Production host: Homo sapiens (human)
#4: Antibody Coltuximab Light Chain


Mass: 23211.758 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Plasmid: pd2610-v5 / Cell line (production host): Expi293F / Production host: Homo sapiens (human)
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Complex of B cell co-receptor CD19 bound to the tetraspanin CD81 and coltuximab Fab fragmentCOMPLEXall0MULTIPLE SOURCES
2B cell co-receptor CD19 bound to the tetraspanin CD81COMPLEX#1-#21RECOMBINANT
3coltuximab Fab fragmentCOMPLEX#3-#41RECOMBINANT
Molecular weightValue: 0.110 MDa / Experimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Mus musculus (house mouse)10090
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDCell
12Homo sapiens (human)9606Expi293F
23Homo sapiens (human)9606Expi293F
Buffer solutionpH: 7.4
Buffer component
IDConc.NameFormulaBuffer-ID
1150 mMsodium chlorideNaCl1
220 mM4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidHEPES1
30.05 %(w:v)glyco-diosgeninGDN1
40.005 %(w:v)Cholesteryl hemisuccinateCHS1
SpecimenConc.: 1.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K
Details: Blot for 4.5-5.5 seconds with a blot force of 15-16.

-
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: 105000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm
Specimen holderSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 55 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 6

-
Processing

Software
NameVersionClassification
phenix.real_space_refine1.18rc5_3822refinement
PHENIX1.18rc5_3822refinement
EM software
IDNameVersionCategory
1crYOLOparticle selection
4CTFFIND4CTF correction
10RELION3.0.8initial Euler assignment
11cryoSPARCv2final Euler assignment
12cryoSPARCv2classification
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 2798945
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 244583 / Num. of class averages: 1 / Symmetry type: POINT
Atomic model building

3D fitting-ID: 1 / Source name: PDB / Type: experimental model

IDPDB-IDPdb chain-IDAccession codeInitial refinement model-ID
16AL5

6al5

A6AL51
25TCX

5tcx

5TCX2
36ANI

6ani

H6ANI3
46ANI

6ani

L6ANI3
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 114.72 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00186114
ELECTRON MICROSCOPYf_angle_d0.40638354
ELECTRON MICROSCOPYf_chiral_restr0.0379962
ELECTRON MICROSCOPYf_plane_restr0.00311076
ELECTRON MICROSCOPYf_dihedral_angle_d9.0643865

+
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