- EMDB-17209: Human Complement C3b in complex with Trypanosoma brucei ISG65. -
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基本情報
登録情報
データベース: EMDB / ID: EMD-17209
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
複合体: Complex of Human Complement C3b and T. brucei ISG65
複合体: Human Complement C3b
タンパク質・ペプチド: Complement C3f fragment
タンパク質・ペプチド: Complement C3
複合体: Trypanosoma brucei ISG65
タンパク質・ペプチド: ISG65 G
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
C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / 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 / Activation of C3 and C5 / positive regulation of phagocytosis, engulfment ...C5L2 anaphylatoxin chemotactic receptor binding / oviduct epithelium development / 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 / Activation of C3 and C5 / positive regulation of phagocytosis, engulfment / positive regulation of lipid storage / positive regulation of G protein-coupled receptor signaling pathway / positive regulation of type IIa hypersensitivity / complement receptor mediated signaling pathway / complement-dependent cytotoxicity / positive regulation of D-glucose transmembrane transport / complement activation / complement activation, alternative pathway / endopeptidase inhibitor activity / neuron remodeling / amyloid-beta clearance / B cell activation / positive regulation of vascular endothelial growth factor production / complement activation, classical pathway / Purinergic signaling in leishmaniasis infection / Peptide ligand-binding receptors / Regulation of Complement cascade / Post-translational protein phosphorylation / response to bacterium / fatty acid metabolic process / positive regulation of receptor-mediated endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of angiogenesis / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / azurophil granule lumen / positive regulation of protein phosphorylation / G alpha (i) signalling events / secretory granule lumen / blood microparticle / immune response / G protein-coupled receptor signaling pathway / inflammatory response / receptor ligand activity / 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
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.
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)
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.