登録情報 データベース : EMDB / ID : EMD-21377 構造の表示 ダウンロードとリンクタイトル Cryo-electron microscopy structure of mouse coronavirus spike protein complexed with its murine receptor マップデータCryoEM density map of MHV spike ectodomain complex with its receptor CEACAM1a 詳細 試料複合体 : MHV Spike and CEACAM1a Complex複合体 : Spike glycoproteinタンパク質・ペプチド : Spike glycoprotein複合体 : Carcinoembryonic antigen-related cell adhesion molecule 1タンパク質・ペプチド : Carcinoembryonic antigen-related cell adhesion molecule 1リガンド : 2-acetamido-2-deoxy-beta-D-glucopyranose 詳細 キーワード MHV spike / CEACAM1a / Complex / Glycoprotein / Viral protein機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
positive regulation of activation-induced cell death of T cells / CD4-positive, alpha-beta T cell activation / Fibronectin matrix formation / granulocyte colony-stimulating factor receptor binding / Post-translational modification: synthesis of GPI-anchored proteins / regulation of endothelial cell differentiation / insulin receptor internalization / negative regulation of cytotoxic T cell degranulation / calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules / granulocyte colony-stimulating factor signaling pathway ... positive regulation of activation-induced cell death of T cells / CD4-positive, alpha-beta T cell activation / Fibronectin matrix formation / granulocyte colony-stimulating factor receptor binding / Post-translational modification: synthesis of GPI-anchored proteins / regulation of endothelial cell differentiation / insulin receptor internalization / negative regulation of cytotoxic T cell degranulation / calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules / granulocyte colony-stimulating factor signaling pathway / regulation of homophilic cell adhesion / negative regulation of hepatocyte proliferation / regulation of sprouting angiogenesis / regulation of epidermal growth factor receptor signaling pathway / regulation of blood vessel remodeling / negative regulation of lipid biosynthetic process / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of T cell mediated cytotoxicity / regulation of endothelial cell migration / negative regulation of granulocyte differentiation / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / insulin catabolic process / Cell surface interactions at the vascular wall / common myeloid progenitor cell proliferation / negative regulation of interleukin-1 production / Toll-like receptor binding / negative regulation of fatty acid biosynthetic process / positive regulation of vasculogenesis / Peyer's patch development / positive regulation of CD4-positive, alpha-beta T cell activation / positive regulation of calcineurin-NFAT signaling cascade / negative regulation of platelet aggregation / bile acid transmembrane transporter activity / positive regulation of CD4-positive, alpha-beta T cell proliferation / cell-cell junction organization / negative regulation of JNK cascade / negative regulation of vascular permeability / virion binding / negative regulation of bone resorption / wound healing, spreading of cells / negative regulation of cytokine production / ciliary membrane / positive regulation of immunoglobulin production / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / negative regulation of interleukin-2 production / negative regulation of T cell receptor signaling pathway / microvillus membrane / bile acid and bile salt transport / blood vessel development / homophilic cell adhesion via plasma membrane adhesion molecules / negative regulation of osteoclast differentiation / lateral plasma membrane / regulation of ERK1 and ERK2 cascade / positive regulation of T cell proliferation / transport vesicle / negative regulation of T cell proliferation / Neutrophil degranulation / protein tyrosine kinase binding / basal plasma membrane / negative regulation of protein kinase activity / adherens junction / positive regulation of JNK cascade / regulation of cell growth / cellular response to insulin stimulus / cell junction / cell-cell junction / virus receptor activity / host cell Golgi apparatus / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / calmodulin binding / protein dimerization activity / apical plasma membrane / endocytosis involved in viral entry into host cell / symbiont entry into host cell / external side of plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / cell surface / protein homodimerization activity / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 : / Spike (S) protein S1 subunit, N-terminal domain, murine hepatitis virus-like / Immunoglobulin domain / Spike glycoprotein S2, coronavirus, C-terminal / Coronavirus spike glycoprotein S2, intravirion / Immunoglobulin domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain ... : / Spike (S) protein S1 subunit, N-terminal domain, murine hepatitis virus-like / Immunoglobulin domain / Spike glycoprotein S2, coronavirus, C-terminal / Coronavirus spike glycoprotein S2, intravirion / Immunoglobulin domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 Spike glycoprotein / Cell adhesion molecule CEACAM1 / CEA cell adhesion molecule 1 類似検索 - 構成要素生物種 Murine coronavirus (strain A59) (ウイルス) / Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.94 Å 詳細 データ登録者Shang J / Wan YS 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) R01AI089728 米国
引用ジャーナル : PLoS Pathog / 年 : 2020タイトル : Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry.著者 : Jian Shang / Yushun Wan / Chang Liu / Boyd Yount / Kendra Gully / Yang Yang / Ashley Auerbach / Guiqing Peng / Ralph Baric / Fang Li / 要旨 : Coronaviruses recognize a variety of receptors using different domains of their envelope-anchored spike protein. How these diverse receptor recognition patterns affect viral entry is unknown. Mouse ... Coronaviruses recognize a variety of receptors using different domains of their envelope-anchored spike protein. How these diverse receptor recognition patterns affect viral entry is unknown. Mouse hepatitis coronavirus (MHV) is the only known coronavirus that uses the N-terminal domain (NTD) of its spike to recognize a protein receptor, CEACAM1a. Here we determined the cryo-EM structure of MHV spike complexed with mouse CEACAM1a. The trimeric spike contains three receptor-binding S1 heads sitting on top of a trimeric membrane-fusion S2 stalk. Three receptor molecules bind to the sides of the spike trimer, where three NTDs are located. Receptor binding induces structural changes in the spike, weakening the interactions between S1 and S2. Using protease sensitivity and negative-stain EM analyses, we further showed that after protease treatment of the spike, receptor binding facilitated the dissociation of S1 from S2, allowing S2 to transition from pre-fusion to post-fusion conformation. Together these results reveal a new role of receptor binding in MHV entry: in addition to its well-characterized role in viral attachment to host cells, receptor binding also induces the conformational change of the spike and hence the fusion of viral and host membranes. Our study provides new mechanistic insight into coronavirus entry and highlights the diverse entry mechanisms used by different viruses. 履歴 登録 2020年2月11日 - ヘッダ(付随情報) 公開 2020年3月4日 - マップ公開 2020年3月4日 - 更新 2024年11月6日 - 現状 2024年11月6日 処理サイト : RCSB / 状態 : 公開
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