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- EMDB-22344: Structure of human CD19-CD81 co-receptor complex bound to coltuxi... -

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Basic information

Entry
Database: EMDB / ID: EMD-22344
TitleStructure of human CD19-CD81 co-receptor complex bound to coltuximab Fab fragment
Map data
SampleComplex of B cell co-receptor CD19 bound to the tetraspanin CD81 and coltuximab Fab fragment
  • B cell co-receptor CD19 bound to the tetraspanin CD81
  • coltuximab Fab fragment
  • B-lymphocyte antigen CD19
  • CD81 antigen
  • Coltuximab Heavy Chain
  • Coltuximab Light Chain
Function / homology
Function and homology information


regulation of B cell activation / antigen receptor-mediated signaling pathway / regulation of macrophage migration / positive regulation of adaptive immune memory response / positive regulation of protein catabolic process in the vacuole / positive regulation of 1-phosphatidylinositol 4-kinase activity / CD4-positive, alpha-beta T cell costimulation / B-1 B cell differentiation / osteoclast fusion / positive regulation of inflammatory response to antigenic stimulus ...regulation of B cell activation / antigen receptor-mediated signaling pathway / regulation of macrophage migration / positive regulation of adaptive immune memory response / positive regulation of protein catabolic process in the vacuole / positive regulation of 1-phosphatidylinositol 4-kinase activity / CD4-positive, alpha-beta T cell costimulation / B-1 B cell differentiation / osteoclast fusion / positive regulation of inflammatory response to antigenic stimulus / myoblast fusion involved in skeletal muscle regeneration / positive regulation of B cell receptor signaling pathway / 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 / macrophage fusion / positive regulation of T-helper 2 cell cytokine production / protein localization to lysosome / positive regulation of protein exit from endoplasmic reticulum / immunological synapse formation / positive regulation of CD4-positive, alpha-beta T cell proliferation / tetraspanin-enriched microdomain / transferrin receptor binding / B cell proliferation involved in immune response / MHC class II protein binding / positive regulation of T cell receptor signaling pathway / cholesterol binding / humoral immune response mediated by circulating immunoglobulin / immunoglobulin mediated immune response / positive regulation of phosphatidylinositol 3-kinase activity / immunological synapse / cellular response to low-density lipoprotein particle stimulus / positive regulation of B cell proliferation / MHC class II protein complex binding / positive regulation of receptor clustering / basal plasma membrane / receptor-mediated virion attachment to host cell / positive regulation of release of sequestered calcium ion into cytosol / protein localization to plasma membrane / protein localization / receptor internalization / regulation of complement activation / regulation of protein stability / B cell receptor signaling pathway / virus receptor activity / positive regulation of peptidyl-tyrosine phosphorylation / integrin binding / regulation of immune response / basolateral plasma membrane / vesicle / activation of MAPK activity / viral entry into host cell / positive regulation of protein kinase B signaling / external side of plasma membrane / membrane raft / focal adhesion / positive regulation of cell population proliferation / integral component of plasma membrane / positive regulation of transcription by RNA polymerase II / protein-containing complex / extracellular exosome / membrane / integral component of membrane / plasma membrane
Tetraspanin, conserved site / Immunoglobulin subtype / Immunoglobulin-like domain / Tetraspanin, EC2 domain superfamily / Tetraspanin / Immunoglobulin-like fold / Tetraspanin/Peripherin / B-lymphocyte antigen CD19 / Immunoglobulin-like domain superfamily
B-lymphocyte antigen CD19 / CD81 antigen
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsSusa KJ / Rawson S / Kruse AC / Blacklow SC
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL 147459 United States
National Institutes of Health/Office of the DirectorDP5 OD021345 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R35 CA220340 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.
Validation ReportSummary, Full report, XML, About validation report
History
DepositionJul 23, 2020-
Header (metadata) releaseJan 20, 2021-
Map releaseJan 20, 2021-
UpdateJan 20, 2021-
Current statusJan 20, 2021Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.27
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by height
  • Surface level: 0.27
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7jic
  • Surface level: 0.3
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_22344.map.gz / Format: CCP4 / Size: 155.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 344 pix.
= 283.8 Å
0.83 Å/pix.
x 344 pix.
= 283.8 Å
0.83 Å/pix.
x 344 pix.
= 283.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.825 Å
Density
Contour LevelBy AUTHOR: 0.359 / Movie #1: 0.27
Minimum - Maximum-1.1148511 - 1.9569672
Average (Standard dev.)0.0018598629 (±0.033939283)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions344344344
Spacing344344344
CellA=B=C: 283.8 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.8250.8250.825
M x/y/z344344344
origin x/y/z0.0000.0000.000
length x/y/z283.800283.800283.800
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ300300300
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS344344344
D min/max/mean-1.1151.9570.002

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Supplemental data

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Half map: #1

Fileemd_22344_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_22344_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire Complex of B cell co-receptor CD19 bound to the tetraspanin CD81 ...

EntireName: Complex of B cell co-receptor CD19 bound to the tetraspanin CD81 and coltuximab Fab fragment
Number of components: 7

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Component #1: protein, Complex of B cell co-receptor CD19 bound to the tetraspa...

ProteinName: Complex of B cell co-receptor CD19 bound to the tetraspanin CD81 and coltuximab Fab fragment
Recombinant expression: No
MassTheoretical: 110 kDa

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Component #2: protein, B cell co-receptor CD19 bound to the tetraspanin CD81

ProteinName: B cell co-receptor CD19 bound to the tetraspanin CD81 / Recombinant expression: No
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human) / Cell of expression system: Expi293F

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Component #3: protein, coltuximab Fab fragment

ProteinName: coltuximab Fab fragment / Recombinant expression: No
SourceSpecies: Mus musculus (house mouse)
Source (engineered)Expression System: Homo sapiens (human) / Cell of expression system: Expi293F

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Component #4: protein, B-lymphocyte antigen CD19

ProteinName: B-lymphocyte antigen CD19 / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 36.031578 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human)

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Component #5: protein, CD81 antigen

ProteinName: CD81 antigen / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 26.444758 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human)

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Component #6: protein, Coltuximab Heavy Chain

ProteinName: Coltuximab Heavy Chain / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 24.828639 kDa
SourceSpecies: Mus musculus (house mouse)
Source (engineered)Expression System: Homo sapiens (human)

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Component #7: protein, Coltuximab Light Chain

ProteinName: Coltuximab Light Chain / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 23.211758 kDa
SourceSpecies: Mus musculus (house mouse)
Source (engineered)Expression System: Homo sapiens (human)

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Experimental details

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Sample preparation

SpecimenSpecimen state: Particle / Method: cryo EM
Sample solutionSpecimen conc.: 1.8 mg/mL / pH: 7.4
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Temperature: 295 K / Humidity: 100 %
Details: Blot for 4.5-5.5 seconds with a blot force of 15-16..

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 55 e/Å2 / Illumination mode: FLOOD BEAM
LensMagnification: 105000 X (nominal) / Cs: 2.7 mm / Imaging mode: BRIGHT FIELD / Defocus: 1000.0 - 2500.0 nm
Specimen HolderModel: FEI TITAN KRIOS AUTOGRID HOLDER
CameraDetector: OTHER

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Image processing

ProcessingMethod: single particle reconstruction / Applied symmetry: C1 (asymmetric) / Number of projections: 244583
3D reconstructionResolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF

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Atomic model buiding

Modeling #1Input PDB model: 6AL5, 5TCX, 6ANI, 6ANI
Chain ID: A, H, L
Output model

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