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キーワード
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

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Structure paper

タイトル	Molecular basis of human CD22 function and therapeutic targeting.
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
著者	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.
リンク	Nat Commun / PubMed:28970495 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.014 - 30.0 Å
構造データ	EMDB-8704: Negative stain electron microscopy map of human CD22 extracellular domain 手法: EM (単粒子) / 解像度: 30.0 Å EMDB-8705: Negative stain electron microscopy map of human CD22 extracellular domain in complex with epratuzumab Fab 手法: EM (単粒子) / 解像度: 30.0 Å PDB-5vkj: Crystal structure of human CD22 Ig domains 1-3 手法: X-RAY DIFFRACTION / 解像度: 2.12 Å PDB-5vkk: Crystal structure of Fab fragment of anti-CD22 Epratuzumab 手法: X-RAY DIFFRACTION / 解像度: 2.014 Å PDB-5vkm: Crystal structure of human CD22 Ig domains 1-3 in complex with alpha 2-6 sialyllactose 手法: X-RAY DIFFRACTION / 解像度: 2.2 Å PDB-5vl3: CD22 d1-d3 in complex with therapeutic Fab Epratuzumab 手法: X-RAY DIFFRACTION / 解像度: 3.1 Å
化合物	ChemComp-GOL: GLYCEROL / グリセロ-ル / グリセリン ChemComp-HOH: WATER / 水
由来	homo sapiens (ヒト) mus musculus (ハツカネズミ)
キーワード	IMMUNE SYSTEM (免疫系) / Siglec (SIGLEC) / Sialic acid (シアル酸) / carbohydrate binding protein / therapeutic antibody / B cell (B細胞) / Fab