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-Structure paper
タイトル | Molecular basis of human CD22 function and therapeutic targeting. |
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ジャーナル・号・ページ | Nat Commun, Vol. 8, Issue 1, Page 764, Year 2017 |
掲載日 | 2017年10月2日 |
![]() | June Ereño-Orbea / Taylor Sicard / Hong Cui / Mohammad T Mazhab-Jafari / Samir Benlekbir / Alba Guarné / John L Rubinstein / Jean-Philippe Julien / ![]() |
PubMed 要旨 | 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. |
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手法 | SAS (X-ray synchrotron) / EM (単粒子) / X線回折 |
解像度 | 2.014 - 30.0 Å |
構造データ | ![]() SASDC76: ![]() SASDC86: ![]() EMDB-8704: ![]() EMDB-8705: ![]() PDB-5vkj: ![]() PDB-5vkk: ![]() PDB-5vkm: ![]() PDB-5vl3: |
化合物 | ![]() ChemComp-GOL: ![]() ChemComp-HOH: |
由来 |
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![]() | IMMUNE SYSTEM / Siglec / Sialic acid / carbohydrate binding protein / therapeutic antibody / B cell / Fab |