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-基本情報
登録情報 | データベース: SASBDB / ID: SASDC76 |
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試料 | Extracellular domain of human B-lymphocyte cell receptor CD22
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機能・相同性 | 機能・相同性情報 regulation of B cell proliferation / IgM binding / negative regulation of immunoglobulin production / negative regulation of B cell receptor signaling pathway / sialic acid binding / CD4 receptor binding / negative regulation of calcium-mediated signaling / CD22 mediated BCR regulation / 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 / CD4 receptor binding / negative regulation of calcium-mediated signaling / CD22 mediated BCR regulation / 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 類似検索 - 分子機能 |
生物種 | Homo sapiens (ヒト) |
引用 | ジャーナル: Nat Commun / 年: 2017 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. |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-Data source
SASBDBのページ | SASDC76 |
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-関連構造データ
-外部リンク
「今月の分子」の関連する項目 |
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-モデル
モデル #1404 | タイプ: dummy / ダミー原子の半径: 5.25 A / カイ2乗値: 0.416 Omokage検索でこの集合体の類似形状データを探す (詳細) |
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-試料
試料 | 名称: Extracellular domain of human B-lymphocyte cell receptor CD22 試料濃度: 5.00-5.00 |
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バッファ | 名称: 20 mM Tris 150 mM NaCl / pH: 9 |
要素 #744 | 名称: CD22 / タイプ: protein / 記述: CD22 extracellular domain / 分子量: 90 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: P20273 配列: MSLWLLEGVP MRQAAVTSTS LTIKSVFTRS ELKFSPQWSH HGKIVTCQLQ DADGKFLSND TVQLNVKHTP KLEIKVTPSD AIVREGDSVT MTCEVSSSNP EYTTVSWLKD GTSLKKQNTF TLNLREVTKD QSGKYCCQVS NDVGPGRSEE VFLQVQYAPE PSTVQILHSP ...配列: MSLWLLEGVP MRQAAVTSTS LTIKSVFTRS ELKFSPQWSH HGKIVTCQLQ DADGKFLSND TVQLNVKHTP KLEIKVTPSD AIVREGDSVT MTCEVSSSNP EYTTVSWLKD GTSLKKQNTF TLNLREVTKD QSGKYCCQVS NDVGPGRSEE VFLQVQYAPE PSTVQILHSP AVEGSQVEFL CMSLANPLPT NYTWYHNGKE MQGRTEEKVH IPKILPWHAG TYSCVAENIL GTGQRGPGAE LDVQYPPKKV TTVIQNPMPI REGDTVTLSC NYNSSNPSVT RYEWKPHGAW EEPSLGVLKI QNVGWDNTTI ACAACNSWCS WASPVALNVQ YAPRDVRVRK IKPLSEIHSG NSVSLQCDFS SSHPKEVQFF WEKNGRLLGK ESQLNFDSIS PEDAGSYSCW VNNSIGQTAS KAWTLEVLYA PRRLRVSMSP GDQVMEGKSA TLTCESDANP PVSHYTWFDW NNQSLPYHSQ KLRLEPVKVQ HSGAYWCQGT NSVGKGRSPL STLTVYYSPE TIGRRVAVGL GSCLAILILA ICGLKLQRRW KRTQSQQGLQ ENSSGQSFFV RNKKVRRAPL SEGPHSLGCY NPMMEDGISY TTLRFPEMNI PRTGDAESSE MQRPPPDCDD TVTYSALHKR QVGDYENVIP DFPEDEGIHY SELIQFGVGE RPQAQENVDY VILKHHHHHH H |
-実験情報
ビーム | 設備名称: Advanced Photon Source (APS) 12ID-B SAXS/WAXS / 地域: Argonne, IL / 国: USA / 線源: X-ray synchrotron / 波長: 0.0886 Å / スペクトロメータ・検出器間距離: 3.6 mm | |||||||||||||||||||||
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検出器 | 名称: Pilatus 2M | |||||||||||||||||||||
スキャン | タイトル: Extracellular domain of human B-lymphocyte cell receptor CD22 測定日: 2016年4月21日 / セル温度: 22 °C / 照射時間: 1 sec. / フレーム数: 30 / 単位: 1/A /
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距離分布関数 P(R) | ソフトウェア P(R): GNOM 5.0 / ポイント数: 147 /
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結果 | Experimental MW: 90 kDa / カーブのタイプ: single_conc
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