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Yorodumi- EMDB-8704: Negative stain electron microscopy map of human CD22 extracellula... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8704 | |||||||||
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Title | Negative stain electron microscopy map of human CD22 extracellular domain | |||||||||
Map data | Negative stain EM Map of unliganded human CD22 extracellular domain (d1-d7 Ig domains) | |||||||||
Sample |
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Function / homology | Function and homology information regulation of B cell proliferation / negative regulation of B cell receptor signaling pathway / IgM binding / negative regulation of immunoglobulin production / sialic acid binding / CD22 mediated BCR regulation / negative regulation of calcium-mediated signaling / CD4 receptor binding / B cell activation / neuronal cell body membrane ...regulation of B cell proliferation / negative regulation of B cell receptor signaling pathway / IgM binding / negative regulation of immunoglobulin production / sialic acid binding / CD22 mediated BCR regulation / negative regulation of calcium-mediated signaling / CD4 receptor binding / B cell activation / neuronal cell body membrane / regulation of endocytosis / regulation of immune response / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / recycling endosome / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / protein phosphatase binding / carbohydrate binding / early endosome / cell adhesion / external side of plasma membrane / signaling receptor binding / cell surface / extracellular exosome / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 30.0 Å | |||||||||
Authors | Julien JP / Ereno-Orbea J / Sicard T | |||||||||
Citation | Journal: Nat Commun / Year: 2017 Title: Molecular basis of human CD22 function and therapeutic targeting. Authors: June Ereño-Orbea / Taylor Sicard / Hong Cui / Mohammad T Mazhab-Jafari / Samir Benlekbir / Alba Guarné / John L Rubinstein / Jean-Philippe Julien / Abstract: CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause ...CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers. Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins. The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals. We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement. Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells. Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation. | |||||||||
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_8704.map.gz | 408.9 KB | EMDB map data format | |
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Header (meta data) | emd-8704-v30.xml emd-8704.xml | 7.7 KB 7.7 KB | Display Display | EMDB header |
Images | emd_8704.png | 11.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8704 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8704 | HTTPS FTP |
-Validation report
Summary document | emd_8704_validation.pdf.gz | 77.8 KB | Display | EMDB validaton report |
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Full document | emd_8704_full_validation.pdf.gz | 76.9 KB | Display | |
Data in XML | emd_8704_validation.xml.gz | 494 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8704 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8704 | HTTPS FTP |
-Related 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_8704.map.gz / Format: CCP4 / Size: 1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Negative stain EM Map of unliganded human CD22 extracellular domain (d1-d7 Ig domains) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.7 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : human CD22 B-cell receptor
Entire | Name: human CD22 B-cell receptor |
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Components |
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-Supramolecule #1: human CD22 B-cell receptor
Supramolecule | Name: human CD22 B-cell receptor / type: organelle_or_cellular_component / ID: 1 / Parent: 0 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Experimental: 90 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | negative staining |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.03 mg/mL |
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Buffer | pH: 9 |
Staining | Type: NEGATIVE / Material: 2% uranyl formate |
-Electron microscopy
Microscope | FEI TECNAI F20 |
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Image recording | Film or detector model: GATAN ORIUS SC200 (2k x 2k) / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Tecnai F20 / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 30.0 Å / Resolution method: OTHER / Number images used: 6312 |
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Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: NOT APPLICABLE |