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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 8q7s | ||||||
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タイトル | Crystal structure of the SARS-CoV-2 RBD (Wuhan) with neutralizing VHHs Ma6F06 and Re21H01 | ||||||
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![]() | ANTIVIRAL PROTEIN / SARS-CoV-2 / VHH Antibody / Nanobody | ||||||
機能・相同性 | ![]() Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() ![]() ![]() | ||||||
手法 | ![]() ![]() ![]() | ||||||
![]() | Guttler, T. / Aksu, M. / Gorlich, D. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Nanobodies to multiple spike variants and inhalation of nanobody-containing aerosols neutralize SARS-CoV-2 in cell culture and hamsters. 著者: Metin Aksu / Priya Kumar / Thomas Güttler / Waltraud Taxer / Kathrin Gregor / Bianka Mußil / Oleh Rymarenko / Kim M Stegmann / Antje Dickmanns / Sabrina Gerber / Wencke Reineking / Claudia ...著者: Metin Aksu / Priya Kumar / Thomas Güttler / Waltraud Taxer / Kathrin Gregor / Bianka Mußil / Oleh Rymarenko / Kim M Stegmann / Antje Dickmanns / Sabrina Gerber / Wencke Reineking / Claudia Schulz / Timo Henneck / Ahmed Mohamed / Gerhard Pohlmann / Mehmet Ramazanoglu / Kemal Mese / Uwe Groß / Tamar Ben-Yedidia / Oded Ovadia / Dalit Weinstein Fischer / Merav Kamensky / Amir Reichman / Wolfgang Baumgärtner / Maren von Köckritz-Blickwede / Matthias Dobbelstein / Dirk Görlich / ![]() ![]() 要旨: The ongoing threat of COVID-19 has highlighted the need for effective prophylaxis and convenient therapies, especially for outpatient settings. We have previously developed highly potent single- ...The ongoing threat of COVID-19 has highlighted the need for effective prophylaxis and convenient therapies, especially for outpatient settings. We have previously developed highly potent single-domain (VHH) antibodies, also known as nanobodies, that target the Receptor Binding Domain (RBD) of the SARS-CoV-2 Spike protein and neutralize the Wuhan strain of the virus. In this study, we present a new generation of anti-RBD nanobodies with superior properties. The primary representative of this group, Re32D03, neutralizes Alpha to Delta as well as Omicron BA.2.75; other members neutralize, in addition, Omicron BA.1, BA.2, BA.4/5, and XBB.1. Crystal structures of RBD-nanobody complexes reveal how ACE2-binding is blocked and also explain the nanobodies' tolerance to immune escape mutations. Through the cryo-EM structure of the Ma16B06-BA.1 Spike complex, we demonstrated how a single nanobody molecule can neutralize a trimeric spike. We also describe a method for large-scale production of these nanobodies in Pichia pastoris, and for formulating them into aerosols. Exposing hamsters to these aerosols, before or even 24 h after infection with SARS-CoV-2, significantly reduced virus load, weight loss and pathogenicity. These results show the potential of aerosolized nanobodies for prophylaxis and therapy of coronavirus infections. #1: ジャーナル: Acta Crystallogr D Struct Biol / 年: 2019 タイトル: Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. 著者: Dorothee Liebschner / Pavel V Afonine / Matthew L Baker / Gábor Bunkóczi / Vincent B Chen / Tristan I Croll / Bradley Hintze / Li Wei Hung / Swati Jain / Airlie J McCoy / Nigel W Moriarty / ...著者: Dorothee Liebschner / Pavel V Afonine / Matthew L Baker / Gábor Bunkóczi / Vincent B Chen / Tristan I Croll / Bradley Hintze / Li Wei Hung / Swati Jain / Airlie J McCoy / Nigel W Moriarty / Robert D Oeffner / Billy K Poon / Michael G Prisant / Randy J Read / Jane S Richardson / David C Richardson / Massimo D Sammito / Oleg V Sobolev / Duncan H Stockwell / Thomas C Terwilliger / Alexandre G Urzhumtsev / Lizbeth L Videau / Christopher J Williams / Paul D Adams / ![]() ![]() ![]() 要旨: Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological ...Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological processes and to develop new therapeutics against diseases. The overall structure-solution workflow is similar for these techniques, but nuances exist because the properties of the reduced experimental data are different. Software tools for structure determination should therefore be tailored for each method. Phenix is a comprehensive software package for macromolecular structure determination that handles data from any of these techniques. Tasks performed with Phenix include data-quality assessment, map improvement, model building, the validation/rebuilding/refinement cycle and deposition. Each tool caters to the type of experimental data. The design of Phenix emphasizes the automation of procedures, where possible, to minimize repetitive and time-consuming manual tasks, while default parameters are chosen to encourage best practice. A graphical user interface provides access to many command-line features of Phenix and streamlines the transition between programs, project tracking and re-running of previous tasks. #2: ジャーナル: Acta Crystallogr D Biol Crystallogr / 年: 2012 タイトル: Towards automated crystallographic structure refinement with phenix.refine. 著者: Afonine, P.V. / Grosse-Kunstleve, R.W. / Echols, N. / Headd, J.J. / Moriarty, N.W. / Mustyakimov, M. / Terwilliger, T.C. / Urzhumtsev, A. / Zwart, P.H. / Adams, P.D. #4: ジャーナル: Acta Crystallogr D Biol Crystallogr / 年: 2007 タイトル: Solving structures of protein complexes by molecular replacement with Phaser. 著者: McCoy, A.J. #5: ジャーナル: Acta Crystallogr D Biol Crystallogr / 年: 2010 タイトル: Features and development of Coot. 著者: P Emsley / B Lohkamp / W G Scott / K Cowtan / ![]() 要旨: Coot is a molecular-graphics application for model building and validation of biological macromolecules. The program displays electron-density maps and atomic models and allows model manipulations ...Coot is a molecular-graphics application for model building and validation of biological macromolecules. The program displays electron-density maps and atomic models and allows model manipulations such as idealization, real-space refinement, manual rotation/translation, rigid-body fitting, ligand search, solvation, mutations, rotamers and Ramachandran idealization. Furthermore, tools are provided for model validation as well as interfaces to external programs for refinement, validation and graphics. The software is designed to be easy to learn for novice users, which is achieved by ensuring that tools for common tasks are 'discoverable' through familiar user-interface elements (menus and toolbars) or by intuitive behaviour (mouse controls). Recent developments have focused on providing tools for expert users, with customisable key bindings, extensions and an extensive scripting interface. The software is under rapid development, but has already achieved very widespread use within the crystallographic community. The current state of the software is presented, with a description of the facilities available and of some of the underlying methods employed. | ||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 513 KB | 表示 | ![]() |
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PDB形式 | ![]() | 338.9 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 563.4 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 580.7 KB | 表示 | |
XML形式データ | ![]() | 73 KB | 表示 | |
CIF形式データ | ![]() | 99.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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単位格子 |
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要素
-タンパク質 , 1種, 5分子 ADGJM
#1: タンパク質 | 分子量: 21949.504 Da / 分子数: 5 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: S, 2 / 発現宿主: ![]() |
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-抗体 , 2種, 10分子 BEHKNCFILO
#2: 抗体 | 分子量: 12350.703 Da / 分子数: 5 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #3: 抗体 | 分子量: 14052.618 Da / 分子数: 5 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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-非ポリマー , 4種, 228分子 ![](data/chem/img/P4G.gif)
![](data/chem/img/EDO.gif)
![](data/chem/img/GOL.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/EDO.gif)
![](data/chem/img/GOL.gif)
![](data/chem/img/HOH.gif)
#4: 化合物 | ChemComp-P4G / | ||||
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#5: 化合物 | ChemComp-EDO / #6: 化合物 | #7: 水 | ChemComp-HOH / | |
-詳細
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: ![]() |
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試料調製
結晶 | マシュー密度: 2.64 Å3/Da / 溶媒含有率: 53.44 % |
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結晶化 | 温度: 293.15 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 4.5 / 詳細: 0.1 M Sodium Citrate pH 4.5 20% (w/v) PEG 4000 |
-データ収集
回折 | 平均測定温度: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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放射光源 | 由来: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
検出器 | タイプ: DECTRIS EIGER X 16M / 検出器: PIXEL / 日付: 2022年4月4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: 1 Å / 相対比: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
反射 | 解像度: 2.48→48.25 Å / Num. obs: 161468 / % possible obs: 91.6 % / 冗長度: 3 % / Biso Wilson estimate: 56.79 Å2 / CC1/2: 0.989 / Rmerge(I) obs: 0.14 / Rrim(I) all: 0.169 / Net I/σ(I): 6.02 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
反射 シェル |
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解析
ソフトウェア |
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精密化 | 構造決定の手法: ![]() 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2
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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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 60.59 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 2.7→48.25 Å
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拘束条件 |
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LS精密化 シェル |
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