+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-17209 | |||||||||
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タイトル | Human Complement C3b in complex with Trypanosoma brucei ISG65. | |||||||||
マップデータ | Human Complement C3 in complex with T. brucei ISG65. Composite map from local alignments of the CUB-TED-ISG65 and remaining C3b regions. Postprocessed in DeepEMhancer. | |||||||||
試料 |
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キーワード | Complement system / parasite virulence / trypanosome surface protein / host-pathogen complex / IMMUNE SYSTEM | |||||||||
機能・相同性 | 機能・相同性情報 oviduct epithelium development / C5L2 anaphylatoxin chemotactic receptor binding / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation / positive regulation of lipid storage / positive regulation of phagocytosis, engulfment ...oviduct epithelium development / C5L2 anaphylatoxin chemotactic receptor binding / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation / positive regulation of lipid storage / positive regulation of phagocytosis, engulfment / positive regulation of G protein-coupled receptor signaling pathway / complement receptor mediated signaling pathway / Activation of C3 and C5 / positive regulation of type IIa hypersensitivity / positive regulation of glucose transmembrane transport / complement-dependent cytotoxicity / complement activation, alternative pathway / complement activation / endopeptidase inhibitor activity / neuron remodeling / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / Purinergic signaling in leishmaniasis infection / fatty acid metabolic process / Peptide ligand-binding receptors / complement activation, classical pathway / Regulation of Complement cascade / Post-translational protein phosphorylation / response to bacterium / positive regulation of receptor-mediated endocytosis / positive regulation of angiogenesis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / azurophil granule lumen / G alpha (i) signalling events / secretory granule lumen / blood microparticle / positive regulation of protein phosphorylation / inflammatory response / immune response / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / signaling receptor binding / Neutrophil degranulation / cell surface / signal transduction / protein-containing complex / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Trypanosoma brucei brucei (トリパノソーマ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.4 Å | |||||||||
データ登録者 | Cook AD / Higgins MK | |||||||||
資金援助 | 英国, 1件
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引用 | ジャーナル: Elife / 年: 2024 タイトル: Molecular mechanism of complement inhibition by the trypanosome receptor ISG65. 著者: Alexander D Cook / Mark Carrington / Matthew K Higgins / 要旨: African trypanosomes replicate within infected mammals where they are exposed to the complement system. This system centres around complement C3, which is present in a soluble form in serum but ...African trypanosomes replicate within infected mammals where they are exposed to the complement system. This system centres around complement C3, which is present in a soluble form in serum but becomes covalently deposited onto the surfaces of pathogens after proteolytic cleavage to C3b. Membrane-associated C3b triggers different complement-mediated effectors which promote pathogen clearance. To counter complement-mediated clearance, African trypanosomes have a cell surface receptor, ISG65, which binds to C3b and which decreases the rate of trypanosome clearance in an infection model. However, the mechanism by which ISG65 reduces C3b function has not been determined. We reveal through cryogenic electron microscopy that ISG65 has two distinct binding sites for C3b, only one of which is available in C3 and C3d. We show that ISG65 does not block the formation of C3b or the function of the C3 convertase which catalyses the surface deposition of C3b. However, we show that ISG65 forms a specific conjugate with C3b, perhaps acting as a decoy. ISG65 also occludes the binding sites for complement receptors 2 and 3, which may disrupt recruitment of immune cells, including B cells, phagocytes, and granulocytes. This suggests that ISG65 protects trypanosomes by combining multiple approaches to dampen the complement cascade. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_17209.map.gz | 118.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-17209-v30.xml emd-17209.xml | 19.2 KB 19.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_17209.png | 158.7 KB | ||
Filedesc metadata | emd-17209.cif.gz | 7.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-17209 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17209 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_17209_validation.pdf.gz | 359.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_17209_full_validation.pdf.gz | 359.1 KB | 表示 | |
XML形式データ | emd_17209_validation.xml.gz | 6.7 KB | 表示 | |
CIF形式データ | emd_17209_validation.cif.gz | 7.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17209 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17209 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_17209.map.gz / 形式: CCP4 / 大きさ: 144.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Human Complement C3 in complex with T. brucei ISG65. Composite map from local alignments of the CUB-TED-ISG65 and remaining C3b regions. Postprocessed in DeepEMhancer. | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.832 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-試料の構成要素
-全体 : Complex of Human Complement C3b and T. brucei ISG65
全体 | 名称: Complex of Human Complement C3b and T. brucei ISG65 |
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要素 |
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-超分子 #1: Complex of Human Complement C3b and T. brucei ISG65
超分子 | 名称: Complex of Human Complement C3b and T. brucei ISG65 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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分子量 | 理論値: 44.2 KDa |
-超分子 #2: Human Complement C3b
超分子 | 名称: Human Complement C3b / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1-#2 詳細: C3 purified from human serum, C3b generated from C3 by limited trypsin proteolysis. |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 組織: Blood |
-超分子 #3: Trypanosoma brucei ISG65
超分子 | 名称: Trypanosoma brucei ISG65 / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #3 |
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由来(天然) | 生物種: Trypanosoma brucei brucei (トリパノソーマ) |
-分子 #1: Complement C3f fragment
分子 | 名称: Complement C3f fragment / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 組織: Blood |
分子量 | 理論値: 71.154047 KDa |
配列 | 文字列: SPMYSIITPN ILRLESEETM VLEAHDAQGD VPVTVTVHDF PGKKLVLSSE KTVLTPATNH MGNVTFTIPA NREFKSEKGR NKFVTVQAT FGTQVVEKVV LVSLQSGYLF IQTDKTIYTP GSTVLYRIFT VNHKLLPVGR TVMVNIENPE GIPVKQDSLS S QNQLGVLP ...文字列: SPMYSIITPN ILRLESEETM VLEAHDAQGD VPVTVTVHDF PGKKLVLSSE KTVLTPATNH MGNVTFTIPA NREFKSEKGR NKFVTVQAT FGTQVVEKVV LVSLQSGYLF IQTDKTIYTP GSTVLYRIFT VNHKLLPVGR TVMVNIENPE GIPVKQDSLS S QNQLGVLP LSWDIPELVN MGQWKIRAYY ENSPQQVFST EFEVKEYVLP SFEVIVEPTE KFYYIYNEKG LEVTITARFL YG KKVEGTA FVIFGIQDGE QRISLPESLK RIPIEDGSGE VVLSRKVLLD GVQNPRAEDL VGKSLYVSAT VILHSGSDMV QAE RSGIPI VTSPYQIHFT KTPKYFKPGM PFDLMVFVTN PDGSPAYRVP VAVQGEDTVQ SLTQGDGVAK LSINTHPSQK PLSI TVRTK KQELSEAEQA TRTMQALPYS TVGNSNNYLH LSVLRTELRP GETLNVNFLL RMDRAHEAKI RYYTYLIMNK GRLLK AGRQ VREPGQDLVV LPLSITTDFI PSFRLVAYYT LIGASGQREV VADSVWVDVK DSCVGSLVVK SGQSEDRQPV PGQQMT LKI EGDHGARVVL VAVDKGVFVL NKKNKLTQSK IWDVVEKADI GCTPGSGKDY AGVFSDAGLT FTSSSGQQTA QRAELQC PQ UniProtKB: Complement C3 |
-分子 #2: Complement C3
分子 | 名称: Complement C3 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 組織: Blood |
分子量 | 理論値: 104.073164 KDa |
配列 | 文字列: SNLDEDIIAE ENIVSRSEFP ESWLWNVEDL KEPPKNGIST KLMNIFLKDS ITTWEILAVS MSDKKGICVA DPFEVTVMQD FFIDLRLPY SVVRNEQVEI RAVLYNYRQN QELKVRVELL HNPAFCSLAT TKRRHQQTVT IPPKSSLSVP YVIVPLKTGL Q EVEVKAAV ...文字列: SNLDEDIIAE ENIVSRSEFP ESWLWNVEDL KEPPKNGIST KLMNIFLKDS ITTWEILAVS MSDKKGICVA DPFEVTVMQD FFIDLRLPY SVVRNEQVEI RAVLYNYRQN QELKVRVELL HNPAFCSLAT TKRRHQQTVT IPPKSSLSVP YVIVPLKTGL Q EVEVKAAV YHHFISDGVR KSLKVVPEGI RMNKTVAVRT LDPERLGREG VQKEDIPPAD LSDQVPDTES ETRILLQGTP VA QMTEDAV DAERLKHLIV TPSGCGEQNM IGMTPTVIAV HYLDETEQWE KFGLEKRQGA LELIKKGYTQ QLAFRQPSSA FAA FVKRAP STWLTAYVVK VFSLAVNLIA IDSQVLCGAV KWLILEKQKP DGVFQEDAPV IHQEMIGGLR NNNEKDMALT AFVL ISLQE AKDICEEQVN SLPGSITKAG DFLEANYMNL QRSYTVAIAG YALAQMGRLK GPLLNKFLTT AKDKNRWEDP GKQLY NVEA TSYALLALLQ LKDFDFVPPV VRWLNEQRYY GGGYGSTQAT FMVFQALAQY QKDAPDHQEL NLDVSLQLPS RSSKIT HRI HWESASLLRS EETKENEGFT VTAEGKGQGT LSVVTMYHAK AKDQLTCNKF DLKVTIKPAP ETEKRPQDAK NTMILEI CT RYRGDQDATM SILDISMMTG FAPDTDDLKQ LANGVDRYIS KYELDKAFSD RNTLIIYLDK VSHSEDDCLA FKVHQYFN V ELIQPGAVKV YAYYNLEESC TRFYHPEKED GKLNKLCRDE LCRCAEENCF IQKSDDKVTL EERLDKACEP GVDYVYKTR LVKVQLSNDF DEYIMAIEQT IKSGSDEVQV GQQRTFISPI KCREALKLEE KKHYLMWGLS SDFWGEKPNL SYIIGKDTWV EHWPEEDEC QDEENQKQCQ DLGAFTESMV VFGCPN UniProtKB: Complement C3 |
-分子 #3: ISG65 G
分子 | 名称: ISG65 G / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Trypanosoma brucei brucei (トリパノソーマ) |
分子量 | 理論値: 32.597322 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: DNRVPGDKNL TKEGAAALCK MKHLADKVAE KRSQELKDRT QNFAGYIEFE LYRIDYWLEK LNGPKGRKDG YAKLSDSDIE KVKEIFDKA KDGIAKQLPE AKKAGEDAEK LHTEVKEAAA NARGQDLDDH KQKSTGLYRV LNWYCITKEE SHNATPNCDG I QFRNHYLS ...文字列: DNRVPGDKNL TKEGAAALCK MKHLADKVAE KRSQELKDRT QNFAGYIEFE LYRIDYWLEK LNGPKGRKDG YAKLSDSDIE KVKEIFDKA KDGIAKQLPE AKKAGEDAEK LHTEVKEAAA NARGQDLDDH KQKSTGLYRV LNWYCITKEE SHNATPNCDG I QFRNHYLS VNRSAIDCSS TGYEENYDWS ANALQVALNS WENVKPKKLE SAGSDENCNI GQSSESHPCT MTEEWQTHYK ET VKKLKEL EGAHEKGRRA HDAMLGYANT AYAVNTKVEQ EKPLAEVIAA AK UniProtKB: ISG65 G |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 2.2 mg/mL | |||||||||
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緩衝液 | pH: 7.4 / 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. / 前処理 - 雰囲気: AIR | |||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 278.15 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Quantum LS / エネルギーフィルター - スリット幅: 20 eV |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 実像数: 14339 / 平均露光時間: 3.03 sec. / 平均電子線量: 49.9 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |