+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7l5j | ||||||
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タイトル | Mouse Norovirus Protruding domain complexed with neutralizing Fab fragment from mAb A6.2 | ||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / Antibody / norovirus / spike / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
機能・相同性 | Calicivirus coat protein C-terminal / Calicivirus coat protein C-terminal / Calicivirus coat protein / Calicivirus coat protein / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / virus-mediated perturbation of host defense response / Capsid protein 機能・相同性情報 | ||||||
生物種 | Murine norovirus 1 (マウスノロウイルス 1) 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: 3.2 Å | ||||||
データ登録者 | Smith, T.J. / Sherman, M.B. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: J Virol / 年: 2021 タイトル: A Norovirus Uses Bile Salts To Escape Antibody Recognition While Enhancing Receptor Binding. 著者: Alexis N Williams / Michael B Sherman / Hong Q Smith / Stefan Taube / B Montgomery Pettitt / Christiane E Wobus / Thomas J Smith / 要旨: Noroviruses, members of the family, are the major cause of epidemic gastroenteritis in humans, causing ∼20 million cases annually. These plus-strand RNA viruses have T=3 icosahedral protein ...Noroviruses, members of the family, are the major cause of epidemic gastroenteritis in humans, causing ∼20 million cases annually. These plus-strand RNA viruses have T=3 icosahedral protein capsids with 90 pronounced protruding (P) domain dimers to which antibodies and cellular receptors bind. In the case of mouse norovirus (MNV), bile salts have been shown to enhance receptor (CD300lf) binding to the P domain. We demonstrated previously that the P domains of several genotypes are markedly flexible and "float" over the shell, but the role of this flexibility was unclear. Recently, we demonstrated that bile causes a 90° rotation and collapse of the P domain onto the shell surface. Since bile binds distally to the P-shell interface, it was not at all clear how it could cause such dramatic changes. Here, we present the near-atomic resolution cryo-electron microscopy (cryo-EM) structure of the MNV protruding domain complexed with a neutralizing Fab. On the basis of previous results, we show here that bile salts cause allosteric conformational changes in the P domain that block antibody recognition of the top of the P domain. In addition, bile causes a major rearrangement of the P domain dimers that is likely responsible for the bile-induced collapse of the P domain onto the shell. In the contracted shell conformation, antibodies to the P1 and shell domains are not expected to bind. Therefore, at the site of infection in the gut, the host's own bile allows the virus to escape antibody-mediated neutralization while enhancing cell attachment. The major feature of calicivirus capsids is the 90 protruding domains (P domains) that are the site of cell receptor attachment and antibody epitopes. We demonstrated previously that these P domains are highly mobile and that bile causes these "floating" P domains in mouse norovirus (MNV) to contract onto the shell surface. Here, we present the near-atomic cryo-EM structure of the isolated MNV P domain complexed with a neutralizing Fab fragment. Our data show that bile causes two sets of changes. First, bile causes allosteric conformational changes in the epitopes at the top of the P domain that block antibody binding. Second, bile causes the P domain dimer subunits to rotate relative to each other, causing a contraction of the P domain that buries epitopes at the base of the P and shell domains. Taken together, the results show that MNV uses the host's own metabolites to enhance cell receptor binding while simultaneously blocking antibody recognition. | ||||||
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 | 7l5j.cif.gz | 252.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7l5j.ent.gz | 209.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7l5j.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/l5/7l5j ftp://data.pdbj.org/pub/pdb/validation_reports/l5/7l5j | HTTPS FTP |
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-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: 34858.281 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) Murine norovirus 1 (マウスノロウイルス 1) 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q2V8W4 #2: 抗体 | 分子量: 23083.512 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Mus musculus (ハツカネズミ) #3: 抗体 | 分子量: 23759.061 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Mus musculus (ハツカネズミ) |
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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) | 生物種: Escherichia coli (大腸菌) | ||||||||||||||||||||||||
ウイルスについての詳細 | 中空か: YES / エンベロープを持つか: NO / 単離: SEROTYPE / タイプ: VIRION | ||||||||||||||||||||||||
天然宿主 | 生物種: Mus musculus | ||||||||||||||||||||||||
ウイルス殻 | 名称: Protein Icosahedron / 三角数 (T数): 3 | ||||||||||||||||||||||||
緩衝液 | pH: 7.4 | ||||||||||||||||||||||||
試料 | 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: 48 e/Å2 / フィルム・検出器のモデル: OTHER |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.15_3448: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1825383 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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