+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 4zjf | |||||||||
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タイトル | Crystal structure of GP1 - the receptor binding domain of Lassa virus | |||||||||
要素 | Glycoprotein糖タンパク質 | |||||||||
キーワード | VIRAL PROTEIN (ウイルスタンパク質) / Arenaviruse / Lassa / receptor binding (受容体) / glycoprotein (糖タンパク質) | |||||||||
機能・相同性 | 機能・相同性情報 host cell Golgi membrane / receptor-mediated endocytosis of virus by host cell / membrane => GO:0016020 / host cell endoplasmic reticulum membrane / fusion of virus membrane with host endosome membrane / エンベロープ (ウイルス) / virion attachment to host cell / host cell plasma membrane / virion membrane / 生体膜 / metal ion binding 類似検索 - 分子機能 | |||||||||
生物種 | Lassa virus Josiah (ウイルス) | |||||||||
手法 | X線回折 / シンクロトロン / 単波長異常分散 / 解像度: 2.595 Å | |||||||||
データ登録者 | Cohen-Dvashi, H. / Cohen, N. / Israeli, H. / Diskin, R. | |||||||||
引用 | ジャーナル: J Virol / 年: 2015 タイトル: Molecular Mechanism for LAMP1 Recognition by Lassa Virus. 著者: Hadas Cohen-Dvashi / Nadav Cohen / Hadar Israeli / Ron Diskin / 要旨: Lassa virus is a notorious human pathogen that infects many thousands of people each year in West Africa, causing severe viral hemorrhagic fevers and significant mortality. The surface glycoprotein ...Lassa virus is a notorious human pathogen that infects many thousands of people each year in West Africa, causing severe viral hemorrhagic fevers and significant mortality. The surface glycoprotein of Lassa virus mediates receptor recognition through its GP1 subunit. Here we report the crystal structure of GP1 from Lassa virus, which is the first representative GP1 structure for Old World arenaviruses. We identify a unique triad of histidines that forms a binding site for LAMP1, a known lysosomal protein recently discovered to be a critical receptor for internalized Lassa virus at acidic pH. We demonstrate that mutation of this histidine triad, which is highly conserved among Old World arenaviruses, impairs LAMP1 recognition. Our biochemical and structural data further suggest that GP1 from Lassa virus may undergo irreversible conformational changes that could serve as an immunological decoy mechanism. Together with a variable region that we identify on the surface of GP1, those could be two distinct mechanisms that Lassa virus utilizes to avoid antibody-based immune response. IMPORTANCE: Structural data at atomic resolution for viral proteins is key for understanding their function at the molecular level and can facilitate novel avenues for combating viral infections. ...IMPORTANCE: Structural data at atomic resolution for viral proteins is key for understanding their function at the molecular level and can facilitate novel avenues for combating viral infections. Here we used X-ray protein crystallography to decipher the crystal structure of the receptor-binding domain (GP1) from Lassa virus. This is a pathogenic virus that causes significant illness and mortality in West Africa. This structure reveals the overall architecture of GP1 domains from the group of viruses known as the Old World arenaviruses. Using this structural information, we elucidated the mechanisms for pH switch and binding of Lassa virus to LAMP1, a recently identified host receptor that is critical for successful infection. Lastly, our structural analysis suggests two novel immune evasion mechanisms that Lassa virus may utilize to escape antibody-based immune response. | |||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 4zjf.cif.gz | 264.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb4zjf.ent.gz | 220.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 4zjf.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/zj/4zjf ftp://data.pdbj.org/pub/pdb/validation_reports/zj/4zjf | 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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単位格子 |
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-要素
#1: タンパク質 | 分子量: 19379.693 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Lassa virus Josiah (ウイルス) / 遺伝子: GPC / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: A0A097F5U5, UniProt: P08669*PLUS #2: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #3: 糖 | ChemComp-NAG / #4: 水 | ChemComp-HOH / | |
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-実験情報
-実験
実験 | 手法: X線回折 |
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-試料調製
結晶 | マシュー密度: 3.03 Å3/Da / 溶媒含有率: 59.35 % |
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結晶化 | 温度: 293 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 5.5 詳細: 0.1 M BisTris pH 5.0, 0.2 M ammonium acetate pH 7.0, 22 % (w/v) PEG 6000 and 5 % (v/v) PEG 200 |
-データ収集
回折 | 平均測定温度: 100 K |
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放射光源 | 由来: シンクロトロン / サイト: ESRF / ビームライン: ID23-2 / 波長: 0.953 Å |
検出器 | タイプ: DECTRIS PILATUS 2M-F / 検出器: PIXEL / 日付: 2014年7月25日 |
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 0.953 Å / 相対比: 1 |
反射 | 解像度: 2.595→49.6 Å / Num. obs: 28667 / % possible obs: 99.1 % / 冗長度: 6.8 % / Rmerge(I) obs: 0.102 / Net I/σ(I): 14.3 |
反射 シェル | 解像度: 2.59→2.68 Å / Rmerge(I) obs: 1.139 / Mean I/σ(I) obs: 1.6 / % possible all: 94.2 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 単波長異常分散 / 解像度: 2.595→49.56 Å / SU ML: 0.35 / 交差検証法: FREE R-VALUE / σ(F): 1.34 / 位相誤差: 27.6 / 立体化学のターゲット値: ML
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å / 溶媒モデル: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 2.595→49.56 Å
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拘束条件 |
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LS精密化 シェル |
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