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Yorodumi- EMDB-22344: Structure of human CD19-CD81 co-receptor complex bound to coltuxi... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22344 | ||||||||||||
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Title | Structure of human CD19-CD81 co-receptor complex bound to coltuximab Fab fragment | ||||||||||||
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Sample |
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Function / homology | Function and homology information regulation of B cell activation / positive regulation of adaptive immune memory response / positive regulation of protein catabolic process in the vacuole / antigen receptor-mediated signaling pathway / CD4-positive, alpha-beta T cell costimulation / osteoclast fusion / B-1 B cell differentiation / positive regulation of B cell receptor signaling pathway / myoblast fusion involved in skeletal muscle regeneration / positive regulation of inflammatory response to antigenic stimulus ...regulation of B cell activation / positive regulation of adaptive immune memory response / positive regulation of protein catabolic process in the vacuole / antigen receptor-mediated signaling pathway / CD4-positive, alpha-beta T cell costimulation / osteoclast fusion / B-1 B cell differentiation / positive regulation of B cell receptor signaling pathway / myoblast fusion involved in skeletal muscle regeneration / positive regulation of inflammatory response to antigenic stimulus / 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 / regulation of macrophage migration / macrophage fusion / transferrin receptor binding / immunological synapse formation / protein localization to lysosome / positive regulation of T-helper 2 cell cytokine production / tetraspanin-enriched microdomain / B cell proliferation involved in immune response / positive regulation of protein exit from endoplasmic reticulum / MHC class II protein binding / humoral immune response mediated by circulating immunoglobulin / positive regulation of CD4-positive, alpha-beta T cell proliferation / cholesterol binding / positive regulation of T cell receptor signaling pathway / cellular response to low-density lipoprotein particle stimulus / immunological synapse / immunoglobulin mediated immune response / positive regulation of B cell proliferation / positive regulation of receptor clustering / basal plasma membrane / positive regulation of release of sequestered calcium ion into cytosol / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / protein localization to plasma membrane / B cell receptor signaling pathway / regulation of protein stability / receptor internalization / Constitutive Signaling by Aberrant PI3K in Cancer / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / integrin binding / PIP3 activates AKT signaling / MHC class II protein complex binding / virus receptor activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / basolateral plasma membrane / vesicle / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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 Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||||||||
Authors | Susa KJ / Rawson S / Kruse AC / Blacklow SC | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: 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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22344.map.gz | 146.6 MB | EMDB map data format | |
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Header (meta data) | emd-22344-v30.xml emd-22344.xml | 22.9 KB 22.9 KB | Display Display | EMDB header |
Images | emd_22344.png | 56.1 KB | ||
Others | emd_22344_half_map_1.map.gz emd_22344_half_map_2.map.gz | 144.1 MB 144.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22344 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22344 | HTTPS FTP |
-Validation report
Summary document | emd_22344_validation.pdf.gz | 919.7 KB | Display | EMDB validaton report |
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Full document | emd_22344_full_validation.pdf.gz | 919.3 KB | Display | |
Data in XML | emd_22344_validation.xml.gz | 14.5 KB | Display | |
Data in CIF | emd_22344_validation.cif.gz | 17 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22344 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22344 | HTTPS FTP |
-Related structure data
Related structure data | 7jicMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_22344.map.gz / Format: CCP4 / Size: 155.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #1
File | emd_22344_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_22344_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of B cell co-receptor CD19 bound to the tetraspanin CD81 ...
Entire | Name: Complex of B cell co-receptor CD19 bound to the tetraspanin CD81 and coltuximab Fab fragment |
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Components |
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-Supramolecule #1: Complex of B cell co-receptor CD19 bound to the tetraspanin CD81 ...
Supramolecule | Name: Complex of B cell co-receptor CD19 bound to the tetraspanin CD81 and coltuximab Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 110 KDa |
-Supramolecule #2: B cell co-receptor CD19 bound to the tetraspanin CD81
Supramolecule | Name: B cell co-receptor CD19 bound to the tetraspanin CD81 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: Expi293F |
-Supramolecule #3: coltuximab Fab fragment
Supramolecule | Name: coltuximab Fab fragment / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: Expi293F |
-Macromolecule #1: B-lymphocyte antigen CD19
Macromolecule | Name: B-lymphocyte antigen CD19 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 36.031578 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DYKDDDDLEV LFQGPPEEPL VVKVEEGDNA VLQCLKGTSD GPTQQLTWSR ESPLKPFLKL SLGLPGLGIH MRPLAIWLFI FNVSQQMGG FYLCQPGPPS EKAWQPGWTV NVEGSGELFR WNVSDLGGLG CGLKNRSSEG PSSPSGKLMS PKLYVWAKDR P EIWEGEPP ...String: DYKDDDDLEV LFQGPPEEPL VVKVEEGDNA VLQCLKGTSD GPTQQLTWSR ESPLKPFLKL SLGLPGLGIH MRPLAIWLFI FNVSQQMGG FYLCQPGPPS EKAWQPGWTV NVEGSGELFR WNVSDLGGLG CGLKNRSSEG PSSPSGKLMS PKLYVWAKDR P EIWEGEPP CLPPRDSLNQ SLSQDLTMAP GSTLWLSCGV PPDSVSRGPL SWTHVHPKGP KSLLSLELKD DRPARDMWVM ET GLLLPRA TAQDAGKYYC HRGNLTMSFH LEITARPVLW HWLLRTGGWK VSAVTLAYLI FCLCSLVGIL HLQRALVLRR KRK RMT |
-Macromolecule #2: CD81 antigen
Macromolecule | Name: CD81 antigen / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 26.444758 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GGSGGSGGSG GSGVEGCTKC IKYLLFVFNF VFWLAGGVIL GVALWLRHDP QTTNLLYLEL GDKPAPNTFY VGIYILIAVG AVMMFVGFL GCYGAIQESQ CLLGTFFTCL VILFACEVAA GIWGFVNKDQ IAKDVKQFYD QALQQAVVDD DANNAKAVVK T FHETLDCC ...String: GGSGGSGGSG GSGVEGCTKC IKYLLFVFNF VFWLAGGVIL GVALWLRHDP QTTNLLYLEL GDKPAPNTFY VGIYILIAVG AVMMFVGFL GCYGAIQESQ CLLGTFFTCL VILFACEVAA GIWGFVNKDQ IAKDVKQFYD QALQQAVVDD DANNAKAVVK T FHETLDCC GSSTLTALTT SVLTSNLCPS GSNIISNLFK EDCHQKIDDL FSGKLYLIGI AAIVVAVIMI FEMILSMVLC CG IRNSSVY |
-Macromolecule #3: Coltuximab Heavy Chain
Macromolecule | Name: Coltuximab Heavy Chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 24.828639 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQPGAE VVKPGASVKL SCKTSGYTFT SNWMHWVKQA PGQGLEWIGE IDPSDSYTNY NQNFQGKAKL TVDKSTSTAY MEVSSLRSD DTAVYYCARG SNPYYYAMDY WGQGTSVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String: QVQLVQPGAE VVKPGASVKL SCKTSGYTFT SNWMHWVKQA PGQGLEWIGE IDPSDSYTNY NQNFQGKAKL TVDKSTSTAY MEVSSLRSD DTAVYYCARG SNPYYYAMDY WGQGTSVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSCGGSGL EVLFQ |
-Macromolecule #4: Coltuximab Light Chain
Macromolecule | Name: Coltuximab Light Chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.211758 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPAI MSASPGERVT MTCSASSGVN YMHWYQQKPG TSPRRWIYDT SKLASGVPAR FSGSGSGTDY SLTISSMEPE DAATYYCHQ RGS(UNK)(UNK)YTFGG GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNA LQSGNS ...String: EIVLTQSPAI MSASPGERVT MTCSASSGVN YMHWYQQKPG TSPRRWIYDT SKLASGVPAR FSGSGSGTDY SLTISSMEPE DAATYYCHQ RGS(UNK)(UNK)YTFGG GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNA LQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.8 mg/mL | |||||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil / Material: COPPER / Mesh: 400 | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV Details: Blot for 4.5-5.5 seconds with a blot force of 15-16.. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 6 / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |