- EMDB-23254: CryoEM structure of the HCMV Trimer gHgLgO in complex with human ... -
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基本情報
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データベース: EMDB / ID: EMD-23254
タイトル
CryoEM structure of the HCMV Trimer gHgLgO in complex with human Transforming growth factor beta receptor type 3 and neutralizing fabs 13H11 and MSL-109
マップデータ
Composite map of Trimer-TGFBR3 complex bound to fabs 13H11 and Msl-109 used for model refinements
試料
複合体: HCMV Trimer gHgLgO bound to human receptor TGFbR3 and neutralizing fabs 13H11 and MSL-109
複合体: HCMV Trimer gHgLgO
タンパク質・ペプチド: Envelope glycoprotein H
タンパク質・ペプチド: Envelope glycoprotein L
タンパク質・ペプチド: Envelope glycoprotein O
複合体: neutralizing fabs 13H11 and MSL-109
タンパク質・ペプチド: Transforming growth factor beta receptor type 3
タンパク質・ペプチド: Fab 13H11 light chain
タンパク質・ペプチド: Fab 13H11 heavy chain
タンパク質・ペプチド: Fab MSL-109 light chain
タンパク質・ペプチド: Fab MSL-109 heavy chain
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
キーワード
virus / receptor / complex / neutralizing antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex
機能・相同性
機能・相同性情報
response to luteinizing hormone / transforming growth factor beta receptor complex assembly / epicardium-derived cardiac fibroblast cell development / inhibin-betaglycan-ActRII complex / muscular septum morphogenesis / TGFBR3 regulates activin signaling / definitive erythrocyte differentiation / TGFBR3 regulates FGF2 signaling / response to follicle-stimulating hormone / BMP binding ...response to luteinizing hormone / transforming growth factor beta receptor complex assembly / epicardium-derived cardiac fibroblast cell development / inhibin-betaglycan-ActRII complex / muscular septum morphogenesis / TGFBR3 regulates activin signaling / definitive erythrocyte differentiation / TGFBR3 regulates FGF2 signaling / response to follicle-stimulating hormone / BMP binding / vasculogenesis involved in coronary vascular morphogenesis / transforming growth factor beta receptor activity / TGFBR3 PTM regulation / ventricular compact myocardium morphogenesis / regulation of transforming growth factor beta receptor signaling pathway / secondary palate development / TGFBR3 regulates TGF-beta signaling / cardiac epithelial to mesenchymal transition / transforming growth factor beta receptor binding / type II transforming growth factor beta receptor binding / transforming growth factor beta receptor activity, type III / activin binding / heart trabecula morphogenesis / FGFR1b ligand binding and activation / FGFR1c ligand binding and activation / Signaling by BMP / Signaling by Activin / glycosaminoglycan binding / heart trabecula formation / definitive hemopoiesis / TGFBR3 expression / transforming growth factor beta binding / negative regulation of extracellular matrix assembly / cardiac muscle cell proliferation / positive regulation of cell migration involved in sprouting angiogenesis / ventricular cardiac muscle tissue morphogenesis / ventricular septum morphogenesis / negative regulation of SMAD protein signal transduction / positive regulation of transforming growth factor beta receptor signaling pathway / SMAD binding / fibroblast growth factor binding / outflow tract morphogenesis / TGF-beta receptor signaling activates SMADs / positive regulation of SMAD protein signal transduction / epithelial to mesenchymal transition / BMP signaling pathway / animal organ regeneration / heart morphogenesis / coreceptor activity / positive regulation of cardiac muscle cell proliferation / response to prostaglandin E / negative regulation of canonical NF-kappaB signal transduction / transforming growth factor beta receptor signaling pathway / negative regulation of cell migration / host cell endosome membrane / liver development / HCMV Late Events / PDZ domain binding / negative regulation of transforming growth factor beta receptor signaling pathway / HCMV Early Events / negative regulation of epithelial cell proliferation / transmembrane signaling receptor activity / cell migration / heparin binding / basolateral plasma membrane / host cell Golgi apparatus / entry receptor-mediated virion attachment to host cell / response to hypoxia / receptor complex / intracellular signal transduction / immune response / symbiont entry into host cell / external side of plasma membrane / fusion of virus membrane with host plasma membrane / viral envelope / positive regulation of gene expression / host cell plasma membrane / virion membrane / cell surface / extracellular space / extracellular exosome / extracellular region / plasma membrane / cytosol 類似検索 - 分子機能
Herpesvirus UL74, glycoprotein / Herpes UL74 glycoproteins / Cytomegalovirus glycoprotein L / Cytomegalovirus glycoprotein L / Betaherpesvirus glycoprotein L (gL) domain profile. / Herpesvirus glycoprotein H main domain / Herpesvirus glycoprotein H / Herpesvirus glycoprotein H, C-terminal / Herpesvirus glycoprotein H, C-terminal domain superfamily / Herpesvirus glycoprotein H C-terminal domain ...Herpesvirus UL74, glycoprotein / Herpes UL74 glycoproteins / Cytomegalovirus glycoprotein L / Cytomegalovirus glycoprotein L / Betaherpesvirus glycoprotein L (gL) domain profile. / Herpesvirus glycoprotein H main domain / Herpesvirus glycoprotein H / Herpesvirus glycoprotein H, C-terminal / Herpesvirus glycoprotein H, C-terminal domain superfamily / Herpesvirus glycoprotein H C-terminal domain / : / Zona pellucida domain, conserved site / ZP domain signature. / Zona pellucida, ZP-C domain / ZP-C domain / Zona pellucida (ZP) domain / ZP domain profile. / Zona pellucida domain 類似検索 - ドメイン・相同性
Envelope glycoprotein L / Transforming growth factor beta receptor type 3 / Envelope glycoprotein H / Envelope glycoprotein O 類似検索 - 構成要素
生物種
Human cytomegalovirus HHV-5 (ヘルペスウイルス) / Homo sapiens (ヒト) / Human cytomegalovirus (strain Merlin) (ヘルペスウイルス) / Human cytomegalovirus (ヘルペスウイルス)
ジャーナル: Cell / 年: 2021 タイトル: Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry. 著者: Marc Kschonsak / Lionel Rougé / Christopher P Arthur / Ho Hoangdung / Nidhi Patel / Ingrid Kim / Matthew C Johnson / Edward Kraft / Alexis L Rohou / Avinash Gill / Nadia Martinez-Martin / ...著者: Marc Kschonsak / Lionel Rougé / Christopher P Arthur / Ho Hoangdung / Nidhi Patel / Ingrid Kim / Matthew C Johnson / Edward Kraft / Alexis L Rohou / Avinash Gill / Nadia Martinez-Martin / Jian Payandeh / Claudio Ciferri / 要旨: Human cytomegalovirus (HCMV) infects the majority of the human population and represents the leading viral cause of congenital birth defects. HCMV utilizes the glycoproteins gHgLgO (Trimer) to bind ...Human cytomegalovirus (HCMV) infects the majority of the human population and represents the leading viral cause of congenital birth defects. HCMV utilizes the glycoproteins gHgLgO (Trimer) to bind to platelet-derived growth factor receptor alpha (PDGFRα) and transforming growth factor beta receptor 3 (TGFβR3) to gain entry into multiple cell types. This complex is targeted by potent neutralizing antibodies and represents an important candidate for therapeutics against HCMV. Here, we determine three cryogenic electron microscopy (cryo-EM) structures of the trimer and the details of its interactions with four binding partners: the receptor proteins PDGFRα and TGFβR3 as well as two broadly neutralizing antibodies. Trimer binding to PDGFRα and TGFβR3 is mutually exclusive, suggesting that they function as independent entry receptors. In addition, Trimer-PDGFRα interaction has an inhibitory effect on PDGFRα signaling. Our results provide a framework for understanding HCMV receptor engagement, neutralization, and the development of anti-viral strategies against HCMV.
モデルのタイプ: OTHER 詳細: EM map of HCMV Trimer-13H11-Msl109 used as starting reference
最終 再構成
想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 2.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cisTEM (ver. 1.02) 詳細: Used a score threshold of 0.25 for final 3D reconstruction. Map used for model refinements is a composite map after combining 2 focussed maps with PHENIX 使用した粒子像数: 2737199
PDB-7lbg: CryoEM structure of the HCMV Trimer gHgLgO in complex with human Transforming growth factor beta receptor type 3 and neutralizing fabs 13H11 and MSL-109