ジャーナル: Science / 年: 2014 タイトル: Complement is activated by IgG hexamers assembled at the cell surface. 著者: Christoph A Diebolder / Frank J Beurskens / Rob N de Jong / Roman I Koning / Kristin Strumane / Margaret A Lindorfer / Marleen Voorhorst / Deniz Ugurlar / Sara Rosati / Albert J R Heck / Jan ...著者: Christoph A Diebolder / Frank J Beurskens / Rob N de Jong / Roman I Koning / Kristin Strumane / Margaret A Lindorfer / Marleen Voorhorst / Deniz Ugurlar / Sara Rosati / Albert J R Heck / Jan G J van de Winkel / Ian A Wilson / Abraham J Koster / Ronald P Taylor / Erica Ollmann Saphire / Dennis R Burton / Janine Schuurman / Piet Gros / Paul W H I Parren / 要旨: Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies ...Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies activate the complement cascade, however, is poorly understood. We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade. The interactions between neighboring Fc segments could be manipulated to block, reconstitute, and enhance complement activation and killing of target cells, using all four human IgG subclasses. We offer a general model for understanding antibody-mediated complement activation and the design of antibody therapeutics with enhanced efficacy.
名称: IgG1-005-RGY monoclonal antibody / タイプ: sample / ID: 1000 / 詳細: sample is a mix of monomers and hexamers / 集合状態: one homohexamer / Number unique components: 1
試料ホルダーモデル: SIDE ENTRY, EUCENTRIC / Tilt series - Axis1 - Min angle: -66 ° / Tilt series - Axis1 - Max angle: 66 °
実験機器
モデル: Tecnai F20 / 画像提供: FEI Company
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画像解析
詳細
manual picking of 237 particles from two tomograms (PEET stalkInit), random particle as initial reference, iterative refinement in PEET
最終 再構成
想定した対称性 - 点群: C1 (非対称) / アルゴリズム: OTHER / 解像度のタイプ: BY AUTHOR / 解像度: 22.0 Å / 解像度の算出法: OTHER / ソフトウェア - 名称: IMOD, PEET, TOMOCTF / 詳細: final map was calculated from 200 sub tomograms / 使用したサブトモグラム数: 200