+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6vsj | ||||||
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タイトル | Cryo-electron microscopy structure of mouse coronavirus spike protein complexed with its murine receptor | ||||||
要素 |
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キーワード | VIRAL PROTEIN / MHV spike / CEACAM1a / Complex / Glycoprotein | ||||||
機能・相同性 | 機能・相同性情報 Fibronectin matrix formation / granulocyte colony-stimulating factor receptor binding / positive regulation of homophilic cell adhesion / Post-translational modification: synthesis of GPI-anchored proteins / regulation of endothelial cell differentiation / insulin receptor internalization / negative regulation of cytotoxic T cell degranulation / granulocyte colony-stimulating factor signaling pathway / regulation of homophilic cell adhesion / regulation of sprouting angiogenesis ...Fibronectin matrix formation / granulocyte colony-stimulating factor receptor binding / positive regulation of homophilic cell adhesion / Post-translational modification: synthesis of GPI-anchored proteins / regulation of endothelial cell differentiation / insulin receptor internalization / negative regulation of cytotoxic T cell degranulation / granulocyte colony-stimulating factor signaling pathway / regulation of homophilic cell adhesion / regulation of sprouting angiogenesis / regulation of epidermal growth factor receptor signaling pathway / negative regulation of hepatocyte proliferation / regulation of blood vessel remodeling / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of lipid biosynthetic process / negative regulation of T cell mediated cytotoxicity / regulation of endothelial cell migration / negative regulation of granulocyte differentiation / insulin catabolic process / Cell surface interactions at the vascular wall / common myeloid progenitor cell proliferation / Toll-like receptor binding / negative regulation of interleukin-1 production / negative regulation of fatty acid biosynthetic process / positive regulation of vasculogenesis / cell-cell adhesion via plasma-membrane adhesion molecules / bile acid transmembrane transporter activity / regulation of immune system process / negative regulation of platelet aggregation / cell-cell junction organization / negative regulation of vascular permeability / negative regulation of bone resorption / bile acid and bile salt transport / wound healing, spreading of cells / ciliary membrane / negative regulation of cytokine production / microvillus membrane / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / negative regulation of T cell receptor signaling pathway / blood vessel development / negative regulation of osteoclast differentiation / lateral plasma membrane / negative regulation of T cell proliferation / transport vesicle / Neutrophil degranulation / regulation of ERK1 and ERK2 cascade / protein tyrosine kinase binding / basal plasma membrane / regulation of cell growth / adherens junction / negative regulation of protein kinase activity / endocytosis involved in viral entry into host cell / cellular response to insulin stimulus / cell-cell junction / cell junction / virus receptor activity / host cell Golgi apparatus / membrane => GO:0016020 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / protein dimerization activity / cell adhesion / calmodulin binding / apical plasma membrane / external side of plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / protein kinase binding / host cell plasma membrane / virion membrane / cell surface / signal transduction / protein homodimerization activity / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Murine coronavirus (ウイルス) Mus musculus (ハツカネズミ) | ||||||
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: 3.94 Å | ||||||
データ登録者 | Shang, J. / Wan, Y.S. / Liu, C. / Yount, B. / Gully, K. / Yang, Y. / Auerbach, A. / Peng, G.Q. / Baric, R. / Li, F. | ||||||
資金援助 | 米国, 1件
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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 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6vsj.cif.gz | 646.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6vsj.ent.gz | 523.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6vsj.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 | 6vsj_validation.pdf.gz | 909.7 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6vsj_full_validation.pdf.gz | 956.4 KB | 表示 | |
XML形式データ | 6vsj_validation.xml.gz | 100.8 KB | 表示 | |
CIF形式データ | 6vsj_validation.cif.gz | 156.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/vs/6vsj ftp://data.pdbj.org/pub/pdb/validation_reports/vs/6vsj | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 141118.797 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) Murine coronavirus (strain A59) (ウイルス) 株: A59 / 遺伝子: S, 3 発現宿主: Baculovirus expression vector pFastBac1-HM (ウイルス) 参照: UniProt: P11224 #2: タンパク質 | 分子量: 23678.691 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Ceacam1, Bgp, Bgp1 発現宿主: Baculovirus expression vector pFastBac1-HM (ウイルス) 参照: UniProt: P31809, UniProt: Q3LFS9*PLUS #3: 糖 | ChemComp-NAG / 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 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.4 | ||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.3 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 77 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
CTF補正 | タイプ: NONE |
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対称性 | 点対称性: C3 (3回回転対称) |
3次元再構成 | 解像度: 3.94 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 82923 / 対称性のタイプ: POINT |