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基本情報
登録情報 | データベース: PDB / ID: 4nm8 | |||||||||
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タイトル | Crystal structure of broadly neutralizing antibody CR8043 bound to H3 influenza hemagglutinin | |||||||||
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![]() | viral protein/immune system / Viral fusion protein / immunoglobulin / virus attachment and entry / immune recognition / viral protein-immune system complex / Immunoglobulin' | |||||||||
機能・相同性 | ![]() IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / CD22 mediated BCR regulation / immunoglobulin complex / IgG immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement ...IgD immunoglobulin complex / IgM immunoglobulin complex / IgA immunoglobulin complex / IgE immunoglobulin complex / CD22 mediated BCR regulation / immunoglobulin complex / IgG immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation / immunoglobulin mediated immune response / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / viral budding from plasma membrane / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / complement activation, classical pathway / Regulation of Complement cascade / Cell surface interactions at the vascular wall / FCERI mediated MAPK activation / FCGR3A-mediated phagocytosis / antigen binding / B cell receptor signaling pathway / Regulation of actin dynamics for phagocytic cup formation / FCERI mediated NF-kB activation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / antibacterial humoral response / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / Potential therapeutics for SARS / blood microparticle / host cell surface receptor binding / immune response / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | ![]() ![]() ![]() | |||||||||
![]() | Lee, P.S. / Wilson, I.A. | |||||||||
![]() | ![]() タイトル: A common solution to group 2 influenza virus neutralization. 著者: Robert H E Friesen / Peter S Lee / Esther J M Stoop / Ryan M B Hoffman / Damian C Ekiert / Gira Bhabha / Wenli Yu / Jarek Juraszek / Wouter Koudstaal / Mandy Jongeneelen / Hans J W M Korse / ...著者: Robert H E Friesen / Peter S Lee / Esther J M Stoop / Ryan M B Hoffman / Damian C Ekiert / Gira Bhabha / Wenli Yu / Jarek Juraszek / Wouter Koudstaal / Mandy Jongeneelen / Hans J W M Korse / Carla Ophorst / Els C M Brinkman-van der Linden / Mark Throsby / Mark J Kwakkenbos / Arjen Q Bakker / Tim Beaumont / Hergen Spits / Ted Kwaks / Ronald Vogels / Andrew B Ward / Jaap Goudsmit / Ian A Wilson / ![]() 要旨: The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the ...The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines. | |||||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 1 MB | 表示 | ![]() |
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PDB形式 | ![]() | 903.1 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2 MB | 表示 | |
XML形式データ | ![]() | 93.6 KB | 表示 | |
CIF形式データ | ![]() | 125.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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単位格子 |
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要素
-Hemagglutinin ... , 2種, 6分子 ACEBDF
#1: タンパク質 | 分子量: 35506.949 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 株: A/Hong Kong/1/1968 H3N2 / 遺伝子: HA / 発現宿主: ![]() #2: タンパク質 | 分子量: 20197.312 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 株: A/Hong Kong/1/1968 H3N2 / 遺伝子: HA / 発現宿主: ![]() |
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-抗体 , 2種, 6分子 LMNHIJ
#3: 抗体 | 分子量: 24228.805 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: 抗体 | 分子量: 24753.713 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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-糖 , 2種, 14分子 ![](data/chem/img/NAG.gif)
#5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #6: 糖 | ChemComp-NAG / |
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-実験情報
-実験
実験 | 手法: ![]() |
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試料調製
結晶 | マシュー密度: 3.39 Å3/Da / 溶媒含有率: 63.73 % |
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結晶化 | 温度: 277 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 5.5 詳細: 2.2 M ammonium sulfate, 0.1 M sodium acetate pH 5.5, 3% PEG 400, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-データ収集
回折 | 平均測定温度: 77 K |
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放射光源 | 由来: ![]() ![]() ![]() |
検出器 | タイプ: PSI PILATUS 6M / 検出器: PIXEL / 日付: 2012年3月22日 |
放射 | モノクロメーター: Liquid nitrogen-cooled double crystal プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 0.9795 Å / 相対比: 1 |
反射 | 解像度: 4→50 Å / Num. all: 34622 / Num. obs: 34622 / % possible obs: 97.7 % / Observed criterion σ(I): -3 / 冗長度: 6.8 % / Biso Wilson estimate: 92.5 Å2 / Rmerge(I) obs: 0.201 / Rsym value: 0.201 / Net I/σ(I): 6.4 |
反射 シェル | 解像度: 4→4.2 Å / 冗長度: 6.5 % / Rmerge(I) obs: 0.826 / Mean I/σ(I) obs: 2.2 / Num. unique all: 4271 / Rsym value: 0.826 / % possible all: 90.8 |
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解析
ソフトウェア |
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精密化 | 構造決定の手法: ![]() 開始モデル: PDB ENTRY 4FNK, 4NM4 解像度: 4.0041→43.821 Å / SU ML: 0.55 / σ(F): 1.99 / 位相誤差: 30.61 / 立体化学のターゲット値: ML
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å / 溶媒モデル: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 4.0041→43.821 Å
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拘束条件 |
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LS精密化 シェル |
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精密化 TLS | 手法: refined / Refine-ID: X-RAY DIFFRACTION
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精密化 TLSグループ |
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