+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7uhb | ||||||
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タイトル | SARS-CoV-2 spike in complex with AHB2-2GS-SB175 (local refinement of the RBD and AHB2) | ||||||
要素 |
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キーワード | VIRAL PROTEIN / SARS-CoV-2 / COVID-19 / spike glycoprotein / fusion protein / neutralizing antibodies / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / Inhibitor | ||||||
機能・相同性 | 機能・相同性情報 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 / symbiont-mediated suppression of host innate immune response / 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 | Severe acute respiratory syndrome coronavirus (SARS コロナウイルス) synthetic construct (人工物) | ||||||
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 Å | ||||||
データ登録者 | Park, Y.J. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler, D. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Sci Transl Med / 年: 2022 タイトル: Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice. 著者: Andrew C Hunt / James Brett Case / Young-Jun Park / Longxing Cao / Kejia Wu / Alexandra C Walls / Zhuoming Liu / John E Bowen / Hsien-Wei Yeh / Shally Saini / Louisa Helms / Yan Ting Zhao / ...著者: Andrew C Hunt / James Brett Case / Young-Jun Park / Longxing Cao / Kejia Wu / Alexandra C Walls / Zhuoming Liu / John E Bowen / Hsien-Wei Yeh / Shally Saini / Louisa Helms / Yan Ting Zhao / Tien-Ying Hsiang / Tyler N Starr / Inna Goreshnik / Lisa Kozodoy / Lauren Carter / Rashmi Ravichandran / Lydia B Green / Wadim L Matochko / Christy A Thomson / Bastian Vögeli / Antje Krüger / Laura A VanBlargan / Rita E Chen / Baoling Ying / Adam L Bailey / Natasha M Kafai / Scott E Boyken / Ajasja Ljubetič / Natasha Edman / George Ueda / Cameron M Chow / Max Johnson / Amin Addetia / Mary-Jane Navarro / Nuttada Panpradist / Michael Gale / Benjamin S Freedman / Jesse D Bloom / Hannele Ruohola-Baker / Sean P J Whelan / Lance Stewart / Michael S Diamond / David Veesler / Michael C Jewett / David Baker / 要旨: New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression ...New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. TRI2-2 neutralized Omicron (B.1.1.529), Delta (B.1.617.2), and all other variants tested with greater potency than the monoclonal antibodies used clinically for the treatment of COVID-19. TRI2-2 also conferred prophylactic and therapeutic protection against SARS-CoV-2 challenge when administered intranasally in mice. Designed miniprotein receptor mimics geometrically arrayed to match pathogen receptor binding sites could be a widely applicable antiviral therapeutic strategy with advantages over antibodies in greater resistance to viral escape and antigenic drift, and advantages over native receptor traps in lower chances of autoimmune responses. | ||||||
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 | 7uhb.cif.gz | 92.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7uhb.ent.gz | 53.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7uhb.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 | 7uhb_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7uhb_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 7uhb_validation.xml.gz | 23.1 KB | 表示 | |
CIF形式データ | 7uhb_validation.cif.gz | 30.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/uh/7uhb ftp://data.pdbj.org/pub/pdb/validation_reports/uh/7uhb | HTTPS FTP |
-関連構造データ
関連構造データ | 26511MC 7uhcC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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: 142427.438 Da / 分子数: 1 / 変異: R682,R683,R685,F817,A892,A899,A942,K986,V987 / 由来タイプ: 組換発現 由来: (組換発現) Severe acute respiratory syndrome coronavirus (SARS コロナウイルス) 遺伝子: S, 2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DTC2 |
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#2: タンパク質 | 分子量: 17565.787 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / 発現宿主: Escherichia coli (大腸菌) |
#3: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose |
研究の焦点であるリガンドがあるか | N |
-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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分子量 | 実験値: NO | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 8 | ||||||||||||||||||||||||
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 / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 500 nm / Cs: 2.7 mm |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア |
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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 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 206541 / 対称性のタイプ: POINT |