[English] 日本語

- PDB-5vkm: Crystal structure of human CD22 Ig domains 1-3 in complex with al... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 5vkm | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Crystal structure of human CD22 Ig domains 1-3 in complex with alpha 2-6 sialyllactose | |||||||||
![]() | B-cell receptor CD22 | |||||||||
![]() | IMMUNE SYSTEM / Siglec / Sialic acid / carbohydrate binding protein | |||||||||
Function / homology | ![]() regulation of B cell proliferation / IgM binding / negative regulation of immunoglobulin production / negative regulation of B cell receptor signaling pathway / sialic acid binding / CD22 mediated BCR regulation / CD4 receptor binding / negative regulation of calcium-mediated signaling / neuronal cell body membrane / B cell activation ...regulation of B cell proliferation / IgM binding / negative regulation of immunoglobulin production / negative regulation of B cell receptor signaling pathway / sialic acid binding / CD22 mediated BCR regulation / CD4 receptor binding / negative regulation of calcium-mediated signaling / neuronal cell body membrane / B cell activation / 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 / carbohydrate binding / protein phosphatase 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 | ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Julien, J.P. / Ereno-Orbea, J. / Sicard, T. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 83 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 58.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 8704C ![]() 8705C ![]() 5vkjSC ![]() 5vkkC ![]() 5vl3C S: Starting model for refinement C: citing same article ( |
---|---|
Similar structure data | |
Other databases |
|
-
Links
-
Assembly
Deposited unit | ![]()
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-
Components
#1: Protein | Mass: 36660.293 Da / Num. of mol.: 1 / Fragment: Extracellular domain residues 20-330 / Mutation: N67A,N112A,N135A,N164A,N231A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
---|---|
#2: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#3: Polysaccharide | N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose Source method: isolated from a genetically manipulated source |
#4: Chemical | ChemComp-GOL / |
#5: Water | ChemComp-HOH / |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|
-
Sample preparation
Crystal | Density Matthews: 2.26 Å3/Da / Density % sol: 45.5 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion Details: 30% PEG 4000, 0.2 M lithium chloride and 0.1 M Tris pH 8.5 |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||
Detector | Type: RAYONIX MX-300 / Detector: CCD / Date: Oct 9, 2016 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97949 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 2.2→36.886 Å / Num. obs: 16865 / % possible obs: 99.6 % / Redundancy: 3.8 % / CC1/2: 0.995 / Rmerge(I) obs: 0.106 / Net I/σ(I): 9.9 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
|
-
Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: ![]() Starting model: 5VKJ Resolution: 2.2→36.886 Å / SU ML: 0.35 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 31.58 / Stereochemistry target values: ML
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.2→36.886 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|