+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5ft2 | |||||||||
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タイトル | Sub-tomogram averaging of Lassa virus glycoprotein spike from virus- like particles at pH 5 | |||||||||
要素 | PRE-GLYCOPROTEIN POLYPROTEIN GP COMPLEX | |||||||||
キーワード | CELL ADHESION / MEMBRANE PROTEIN / GLYCOPROTEIN / RECEPTOR BINDING / MEMBRANE FUSION | |||||||||
機能・相同性 | 機能・相同性情報 host cell Golgi membrane / receptor-mediated endocytosis of virus by host cell / host cell endoplasmic reticulum membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane / metal ion binding 類似検索 - 分子機能 | |||||||||
生物種 | LASSA VIRUS (ウイルス) | |||||||||
手法 | 電子顕微鏡法 / 電子線トモグラフィー法 / クライオ電子顕微鏡法 / 解像度: 16.4 Å | |||||||||
データ登録者 | Li, S. / Zhaoyang, S. / Pryce, R. / Parsy, M.L. / Fehling, S.K. / Schlie, K. / Siebert, C.A. / Garten, W. / Bowden, T.A. / Strecker, T. / Huiskonen, J.T. | |||||||||
引用 | ジャーナル: PLoS Pathog / 年: 2016 タイトル: Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike. 著者: Sai Li / Zhaoyang Sun / Rhys Pryce / Marie-Laure Parsy / Sarah K Fehling / Katrin Schlie / C Alistair Siebert / Wolfgang Garten / Thomas A Bowden / Thomas Strecker / Juha T Huiskonen / 要旨: Lassa virus is an enveloped, bi-segmented RNA virus and the most prevalent and fatal of all Old World arenaviruses. Virus entry into the host cell is mediated by a tripartite surface spike complex, ...Lassa virus is an enveloped, bi-segmented RNA virus and the most prevalent and fatal of all Old World arenaviruses. Virus entry into the host cell is mediated by a tripartite surface spike complex, which is composed of two viral glycoprotein subunits, GP1 and GP2, and the stable signal peptide. Of these, GP1 binds to cellular receptors and GP2 catalyzes fusion between the viral envelope and the host cell membrane during endocytosis. The molecular structure of the spike and conformational rearrangements induced by low pH, prior to fusion, remain poorly understood. Here, we analyzed the three-dimensional ultrastructure of Lassa virus using electron cryotomography. Sub-tomogram averaging yielded a structure of the glycoprotein spike at 14-Å resolution. The spikes are trimeric, cover the virion envelope, and connect to the underlying matrix. Structural changes to the spike, following acidification, support a viral entry mechanism dependent on binding to the lysosome-resident receptor LAMP1 and further dissociation of the membrane-distal GP1 subunits. #1: 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
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 | 5ft2.cif.gz | 75.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5ft2.ent.gz | 58.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5ft2.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 | 5ft2_validation.pdf.gz | 770.8 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 5ft2_full_validation.pdf.gz | 771.3 KB | 表示 | |
XML形式データ | 5ft2_validation.xml.gz | 15.2 KB | 表示 | |
CIF形式データ | 5ft2_validation.cif.gz | 20.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ft/5ft2 ftp://data.pdbj.org/pub/pdb/validation_reports/ft/5ft2 | 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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-要素
#1: タンパク質 | 分子量: 19379.693 Da / 分子数: 1 / 断片: RECEPTOR BINDING DOMAIN, UNP RESIDUES 75-237 / 由来タイプ: 組換発現 / 由来: (組換発現) LASSA VIRUS (ウイルス) / 株: JOSIAH / 発現宿主: TRICHOPLUSIA NI (イラクサキンウワバ) / 参照: UniProt: P08669 | ||||
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#2: 多糖 | #3: 糖 | #4: 水 | ChemComp-HOH / | |
-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: 電子線トモグラフィー法 |
-試料調製
構成要素 | 名称: PURIFIED LASSA VIRUS VLPS AT PH 5 / タイプ: VIRUS |
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緩衝液 | 名称: 50 MM BUFFER OF SUCCINIC ACID, DIHYDROGEN PHOSPHATE AND GLYCINE (SPG) pH: 5.2 詳細: 50 MM BUFFER OF SUCCINIC ACID, DIHYDROGEN PHOSPHATE AND GLYCINE (SPG) |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: HOLEY CARBON |
急速凍結 | 装置: GATAN CRYOPLUNGE 3 / 凍結剤: ETHANE-PROPANE 詳細: VITRIFICATION 1 -- CRYOGEN- ETHANE-PROPANE MIXTURE, HUMIDITY- 80, TEMPERATURE- 120, INSTRUMENT- GATAN CRYOPLUNGE 3, METHOD- BLOT FOR 3 SECONDS BEFORE PLUNGING., |
-電子顕微鏡撮影
実験機器 | モデル: Tecnai F30 / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TECNAI F30 / 日付: 2014年9月25日 / 詳細: SUPER-RESOLUTION COUNTING MODE |
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 / 倍率(公称値): 160000 X / 倍率(補正後): 37037 X / 最大 デフォーカス(公称値): 6700 nm / 最小 デフォーカス(公称値): 2800 nm / Cs: 2 mm |
試料ホルダ | 傾斜角・最大: 45 ° / 傾斜角・最小: -45 ° |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
画像スキャン | デジタル画像の数: 16 |
-解析
EMソフトウェア |
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CTF補正 | 詳細: EACH TILTED IMAGE | ||||||||||||||||||||
対称性 | 点対称性: C3 (3回回転対称) | ||||||||||||||||||||
3次元再構成 | 手法: TEMPLATE BASED / 解像度: 16.4 Å / 粒子像の数: 2578 / ピクセルサイズ(公称値): 2.7 Å / ピクセルサイズ(実測値): 2.7 Å 詳細: SUB-TOMOGRAM AVERAGING SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-3292. (DEPOSITION ID: 14158). 対称性のタイプ: POINT | ||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT / 空間: REAL / Target criteria: Cross-correlation coefficient / 詳細: METHOD--RIGID BODY REFINEMENT PROTOCOL--X-RAY | ||||||||||||||||||||
原子モデル構築 | PDB-ID: 4ZJF | ||||||||||||||||||||
精密化 | 最高解像度: 16.4 Å | ||||||||||||||||||||
精密化ステップ | サイクル: LAST / 最高解像度: 16.4 Å
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