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データを開く
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基本情報
登録情報 | データベース: SASBDB / ID: SASDA48 |
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![]() | transglutaminase2:anti-transglutaminase2 FAB1 antibody complex
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生物種 | ![]() |
![]() | ![]() タイトル: Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease. 著者: Xi Chen / Kathrin Hnida / Melissa Ann Graewert / Jan Terje Andersen / Rasmus Iversen / Anne Tuukkanen / Dmitri Svergun / Ludvig M Sollid / ![]() ![]() 要旨: Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut ...Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease. |
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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
-モデル
モデル #308 | ![]() タイプ: dummy / ソフトウェア: DAMMIN / ダミー原子の半径: 3.50 A / カイ2乗値: 0.724201 / P-value: 0.157000 ![]() |
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モデル #309 | ![]() タイプ: atomic / ソフトウェア: SASREF / ダミー原子の半径: 1.90 A / カイ2乗値: 0.66 / P-value: 0.053000 ![]() |
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試料
![]() | 名称: transglutaminase2:anti-transglutaminase2 FAB1 antibody complex 試料濃度: 9 mg/ml / Entity id: 175 / 176 |
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バッファ | 名称: 20 mM Tris 150mM NaCl 1mM EDTA / 濃度: 20.00 mM / pH: 7.2 / 組成: 150mM NaCl, 1mM EDTA |
要素 #175 | タイプ: protein / 記述: anti-TG2 antibody (679 14 E06) / 分子量: 47.639 / 分子数: 1 配列: EVQLVQSGAE VKKPGESLKI SCKGSGYSFT SYWIGWVRQM PGKGLEWMGI IYPGDSDTRY SPSFQGQVTI SADKSISTAY LQWSSLKASD TAMYYCARPH YYDSLDAFDI WGQGTMVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG ...配列: EVQLVQSGAE VKKPGESLKI SCKGSGYSFT SYWIGWVRQM PGKGLEWMGI IYPGDSDTRY SPSFQGQVTI SADKSISTAY LQWSSLKASD TAMYYCARPH YYDSLDAFDI WGQGTMVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDIQMTQ SPSTLSASVG DRVTITCRAS QSISSWLAWY QQRPGKAPKL LIYKASSLES GVPSRFSGSG SGTEFTLTIS SLQPDDFATY YCQHYNSYSP GYTFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL QSGNSQESVT EQDSKDSTYS LSSTLTLSKA DYEKHKVYAC EVTHQGLSSP VTKSFNRGEC |
要素 #176 | 名称: TGA / タイプ: protein / 記述: transglutaminase 2 / 分子量: 79.491 / 分子数: 1 / 由来: Homo sapiens 配列: MGSSHHHHHH SSGLVPRGSH maeelvlerc dleletngrd hhtadlcrek lvvrrgqpfw ltlhfegrny easvdsltfs vvtgpapsqe agtkarfplr daveegdwta tvvdqqdctl slqlttpana piglyrlsle astgyqgssf vlghfillfn awcpadavyl ...配列: MGSSHHHHHH SSGLVPRGSH maeelvlerc dleletngrd hhtadlcrek lvvrrgqpfw ltlhfegrny easvdsltfs vvtgpapsqe agtkarfplr daveegdwta tvvdqqdctl slqlttpana piglyrlsle astgyqgssf vlghfillfn awcpadavyl dseeerqeyv ltqqgfiyqg sakfiknipw nfgqfedgil diclilldvn pkflknagrd csrrsspvyv grvvsgmvnc nddqgvllgr wdnnygdgvs pmswigsvdi lrrwknhgcq rvkygqcwvf aavactvlrc lgiptrvvtn ynsahdqnsn llieyfrnef geiqgdksem iwnfhcwves wmtrpdlqpg yegwqaldpt pqeksegtyc cgpvpvraik egdlstkyda pfvfaevnad vvdwiqqddg svhksinrsl ivglkistks vgrderedit htykypegss eereaftran hlnklaekee tgmamrirvg qsmnmgsdfd vfahitnnta eeyvcrlllc artvsyngil gpecgtkyll nlnlepfsek svplcilyek yrdcltesnl ikvrallvep vinsyllaer dlylenpeik irilgepkqk rklvaevslq nplpvalegc tftvegaglt eeqktveipd pveageevkv rmdllplhmg lhklvvnfes dklkavkgfr nviigpa |
-実験情報
ビーム | 設備名称: PETRA III P12 / 地域: Hamburg / 国: Germany ![]() | |||||||||||||||||||||||||||||||||||||||
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検出器 | 名称: Pilatus 2M | |||||||||||||||||||||||||||||||||||||||
スキャン |
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距離分布関数 P(R) |
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結果 | コメント: Structural basis for antigen recognition by transglutaminase 2-specific autoantibodies in celiac disease. SAXS profile of the complex formed between transglutaminase2 bound to anti- ...コメント: Structural basis for antigen recognition by transglutaminase 2-specific autoantibodies in celiac disease. SAXS profile of the complex formed between transglutaminase2 bound to anti-transglutaminase2 antibody (679 14 E06) FAB1.
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