5VKJ

Crystal structure of human CD22 Ig domains 1-3

Summary for 5VKJ

• Entry DOI: 10.2210/pdb5vkj/pdb
• Related: 5VKK 5VKM 5VL3
• EMDB information: 8704 8705
• Descriptor: B-cell receptor CD22, 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, GLYCEROL, ... (4 entities in total)
• Functional Keywords: siglec, sialic acid, carbohydrate binding protein, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 37939.49

Authors

Julien, J.P.,Ereno-Orbea, J.,Sicard, T. (deposition date: 2017-04-21, release date: 2017-10-04, Last modification date: 2024-11-20)

Primary citation

Ereno-Orbea, J.,Sicard, T.,Cui, H.,Mazhab-Jafari, M.T.,Benlekbir, S.,Guarne, A.,Rubinstein, J.L.,Julien, J.P.
Molecular basis of human CD22 function and therapeutic targeting.
Nat Commun, 8:764-764, 2017

PubMed 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 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.

PubMed: 28970495
DOI: 10.1038/s41467-017-00836-6

Experimental method

X-RAY DIFFRACTION (2.12 Å)