+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8uin | ||||||
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タイトル | Structure of the C3bBb-albicin complex | ||||||
要素 |
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キーワード | IMMUNE SYSTEM / Complement / Inhibitor / Mosquito / Convertase | ||||||
機能・相同性 | 機能・相同性情報 alternative-complement-pathway C3/C5 convertase / oviduct epithelium development / C5L2 anaphylatoxin chemotactic receptor binding / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / complement binding / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation ...alternative-complement-pathway C3/C5 convertase / oviduct epithelium development / C5L2 anaphylatoxin chemotactic receptor binding / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / complement binding / 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 / serine-type endopeptidase activity / signaling receptor binding / Neutrophil degranulation / cell surface / signal transduction / protein-containing complex / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Anopheles albimanus (カ) Homo sapiens (ヒト) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.86 Å | ||||||
データ登録者 | Andersen, J.F. / Lei, H. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Commun Biol / 年: 2024 タイトル: Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM. 著者: John F Andersen / Haotian Lei / Ethan C Strayer / Van Pham / José M C Ribeiro / 要旨: Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of ...Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of proinflammatory anaphylatoxins, which may interfere with feeding, and limit formation of the membrane attack complex which could damage arthropod gut tissues. Salivary inhibitors are, in many cases, novel proteins which may be pharmaceutically useful or display unusual mechanisms that could be exploited pharmaceutically. Albicin is a potent inhibitor of the alternative pathway of complement from the saliva of the malaria transmitting mosquito, Anopheles albimanus. Here we describe the cryo-EM structure of albicin bound to C3bBb, the alternative C3 convertase, a proteolytic complex that is responsible for cleavage of C3 and amplification of the complement response. Albicin is shown to induce dimerization of C3bBb, in a manner similar to the bacterial inhibitor SCIN, to form an inactive complex unable to bind the substrate C3. Size exclusion chromatography and structures determined after 30 minutes of incubation of C3b, factor B (FB), factor D (FD) and albicin indicate that FBb dissociates from the inhibited dimeric complex leaving a C3b-albicin dimeric complex which apparently decays more slowly. | ||||||
履歴 |
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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
-ダウンロード
PDBx/mmCIF形式 | 8uin.cif.gz | 873.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8uin.ent.gz | 662.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8uin.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 8uin_validation.pdf.gz | 1.5 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8uin_full_validation.pdf.gz | 1.5 MB | 表示 | |
XML形式データ | 8uin_validation.xml.gz | 103 KB | 表示 | |
CIF形式データ | 8uin_validation.cif.gz | 155.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ui/8uin ftp://data.pdbj.org/pub/pdb/validation_reports/ui/8uin | HTTPS FTP |
-関連構造データ
関連構造データ | 42300MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 4種, 8分子 CDJXAGBH
#1: タンパク質 | 分子量: 13461.331 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Anopheles albimanus (カ) / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / Variant (発現宿主): pLysS / 参照: UniProt: A0A1Y9G8D0 #2: タンパク質 | 分子量: 25766.305 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P00751 #3: タンパク質 | 分子量: 71154.047 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P01024 #4: タンパク質 | 分子量: 104073.164 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P01024 |
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-糖 , 2種, 4分子
#5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
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#6: 糖 |
-詳細
研究の焦点であるリガンドがあるか | N |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: complex of C3bBb with the inhibitor albicin / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: MULTIPLE SOURCES |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.4 / 詳細: 10 mM Hepes pH 7.4, 150 mM NaCl, 5 mM MgCl2 |
試料 | 濃度: 1.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: The sample was formed by incubating C3b, factor B, factor D and albicin. The sample was monodisperse |
試料支持 | グリッドの材料: GOLD / グリッドのタイプ: C-flat-1.2/1.3 |
急速凍結 | 装置: FEI VITROBOT MARK III / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 279.15 K |
-電子顕微鏡撮影
顕微鏡 | モデル: TFS GLACIOS |
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電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 200 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2200 nm / 最小 デフォーカス(公称値): 300 nm |
撮影 | 電子線照射量: 66.7 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 492352 | ||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.86 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 65862 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | 空間: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | 3D fitting-ID: 1 / Source name: PDB / タイプ: experimental model
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拘束条件 |
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