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基本情報
登録情報 | データベース: EMDB / ID: EMD-8705 | |||||||||
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タイトル | Negative stain electron microscopy map of human CD22 extracellular domain in complex with epratuzumab Fab | |||||||||
![]() | Negative stain electron microscopy map of CD22 extracellular domain in complex with Fab fragment of epratuzumab | |||||||||
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機能・相同性 | ![]() 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 / 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 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / ネガティブ染色法 / 解像度: 30.0 Å | |||||||||
![]() | Julien JP / Ereno-Orbea J / Sicard T | |||||||||
![]() | ![]() タイトル: Molecular basis of human CD22 function and therapeutic targeting. 著者: June Ereño-Orbea / Taylor Sicard / Hong Cui / Mohammad T Mazhab-Jafari / Samir Benlekbir / Alba Guarné / John L Rubinstein / Jean-Philippe Julien / ![]() 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. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 411.5 KB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 7.8 KB 7.8 KB | 表示 表示 | ![]() |
画像 | ![]() | 9.6 KB | ||
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Negative stain electron microscopy map of CD22 extracellular domain in complex with Fab fragment of epratuzumab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 2.7 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : human CD22 B-cell receptor
全体 | 名称: human CD22 B-cell receptor |
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要素 |
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-超分子 #1: human CD22 B-cell receptor
超分子 | 名称: human CD22 B-cell receptor / タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0 |
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由来(天然) | 生物種: ![]() |
分子量 | 実験値: 90 KDa |
組換発現 | 生物種: ![]() |
-実験情報
-構造解析
手法 | ネガティブ染色法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.03 mg/mL |
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緩衝液 | pH: 9 |
染色 | タイプ: NEGATIVE / 材質: 2% uranyl formate |
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電子顕微鏡法
顕微鏡 | FEI TECNAI F20 |
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撮影 | フィルム・検出器のモデル: GATAN ORIUS SC200 (2k x 2k) 平均電子線量: 30.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: ![]() |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Tecnai F20 / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 30.0 Å / 解像度の算出法: OTHER / 使用した粒子像数: 6312 |
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初期 角度割当 | タイプ: NOT APPLICABLE |
最終 角度割当 | タイプ: NOT APPLICABLE |