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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: 7tz0 | ||||||
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タイトル | Cryo-EM structure of SARS-CoV-2 spike in complex with FSR22, an anti-SARS-CoV-2 DARPin (Local refinement of FSR22 and RBD) | ||||||
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![]() | VIRAL PROTEIN/ANTIVIRAL PROTEIN / DARPins / Anti-SARS-CoV-2 / therapeutics / COVID-19 / VIRAL PROTEIN-ANTIVIRAL PROTEIN complex | ||||||
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 / symbiont-mediated-mediated suppression 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 / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / membrane fusion / Attachment and Entry / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / 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 | 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: 4.17 Å | ||||||
![]() | Kwon, Y.D. / Gorman, J. / Kwong, P.D. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins. 著者: Vikas Chonira / Young D Kwon / Jason Gorman / James Brett Case / Zhiqiang Ku / Rudo Simeon / Ryan G Casner / Darcy R Harris / Adam S Olia / Tyler Stephens / Lawrence Shapiro / Michael F ...著者: Vikas Chonira / Young D Kwon / Jason Gorman / James Brett Case / Zhiqiang Ku / Rudo Simeon / Ryan G Casner / Darcy R Harris / Adam S Olia / Tyler Stephens / Lawrence Shapiro / Michael F Bender / Hannah Boyd / I-Ting Teng / Yaroslav Tsybovsky / Florian Krammer / Ningyan Zhang / Michael S Diamond / Peter D Kwong / Zhiqiang An / Zhilei Chen / ![]() 要旨: We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and ...We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective IC values of 3.4, 2.2 and 7.4 ng ml for FSR16m. Cryo-EM structures revealed that these DARPins recognize a region of the receptor-binding domain (residues 456, 475, 486, 487 and 489) overlapping a critical portion of the angiotensin-converting enzyme 2 (ACE2)-binding surface. K18-hACE2 transgenic mice inoculated with B.1.617.2 and receiving intranasally administered FSR16m showed less weight loss and 10-100-fold lower viral burden in upper and lower respiratory tracts. The strong and broad neutralization potency makes FSR16m and FSR22 promising candidates for the prevention and treatment of infection by SARS-CoV-2. | ||||||
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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 | ![]() | 98.8 KB | 表示 | ![]() |
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PDB形式 | ![]() | 58.3 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 | ![]() | 849.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 853.5 KB | 表示 | |
XML形式データ | ![]() | 15.7 KB | 表示 | |
CIF形式データ | ![]() | 21.7 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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要素
#1: タンパク質 | 分子量: 138236.828 Da / 分子数: 1 / 変異: F817P, A892P, A899P, A942P, K986P, V987P / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: S, 2 / プラスミド: pVRC8400 / 細胞株 (発現宿主): Freestyle 293 / 発現宿主: ![]() |
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#2: タンパク質 | 分子量: 23835.580 Da / 分子数: 1 / 由来タイプ: 合成 / 詳細: Protein selected by phage display 由来: (合成) ![]() |
Has protein modification | Y |
-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 |
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試料調製
構成要素 | 名称: DARPin FSR22 in complex with RBD of SARS-CoV-2 spike タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES | ||||||||||||
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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) | 生物種: ![]() | ||||||||||||
緩衝液 | pH: 7.4 / 詳細: 10 mM HEPES, 7.4, 150 mM NaCl | ||||||||||||
試料 | 濃度: 0.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 95 % |
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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: ![]() |
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): 1250 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm |
撮影 | 電子線照射量: 40.2 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.20_4459: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 417461 | ||||||||||||||||||||||||
3次元再構成 | 解像度: 4.17 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 18892 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | B value: 134 / プロトコル: RIGID BODY FIT / 空間: REAL / Target criteria: CC | ||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 7BNO Accession code: 7BNO / Source name: PDB / タイプ: experimental model | ||||||||||||||||||||||||
拘束条件 |
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