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基本情報
登録情報 | データベース: PDB / ID: 7tez | |||||||||
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タイトル | Cryo-EM structure of SARS-CoV-2 Kappa (B.1.617.1) spike protein in complex with human ACE2 (focused refinement of RBD and ACE2) | |||||||||
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![]() | VIRAL PROTEIN / SARS-CoV-2 / glycoprotein / fusion protein / ACE2 | |||||||||
機能・相同性 | ![]() positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / negative regulation of signaling receptor activity / regulation of vasoconstriction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; 金属プロテアーゼ / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / negative regulation of signaling receptor activity / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / regulation of transmembrane transporter activity / cilium / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / endocytic vesicle membrane / virus receptor activity / regulation of inflammatory response / regulation of cell population proliferation / endopeptidase activity / Potential therapeutics for SARS / 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 / Attachment and Entry / membrane fusion / 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 / apical plasma membrane / symbiont entry into host cell / membrane raft / endoplasmic reticulum lumen / 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 / cell surface / extracellular space / zinc ion binding / extracellular exosome / extracellular region / 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: 3.27 Å | |||||||||
![]() | Zhu, X. / Saville, J.W. / Mannar, D. / Srivastava, S.S. / Berezuk, A.M. / Demers, J.P. / Zhou, S. / Tuttle, K.S. / Subramaniam, S. | |||||||||
資金援助 | 2件
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![]() | ![]() タイトル: Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants. 著者: James W Saville / Dhiraj Mannar / Xing Zhu / Shanti S Srivastava / Alison M Berezuk / Jean-Philippe Demers / Steven Zhou / Katharine S Tuttle / Inna Sekirov / Andrew Kim / Wei Li / Dimiter S ...著者: James W Saville / Dhiraj Mannar / Xing Zhu / Shanti S Srivastava / Alison M Berezuk / Jean-Philippe Demers / Steven Zhou / Katharine S Tuttle / Inna Sekirov / Andrew Kim / Wei Li / Dimiter S Dimitrov / Sriram Subramaniam / ![]() ![]() 要旨: The Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this ...The Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this study, we assess structural and biochemical aspects of viral fitness for these two variants using cryo-electron microscopy (cryo-EM), ACE2-binding and antibody neutralization analyses. Both variants demonstrate escape of antibodies targeting the N-terminal domain, an important immune hotspot for neutralizing epitopes. Compared to wild-type and Kappa lineages, Delta variant spike proteins show modest increase in ACE2 affinity, likely due to enhanced electrostatic complementarity at the RBD-ACE2 interface, which we characterize by cryo-EM. Unexpectedly, Kappa variant spike trimers form a structural head-to-head dimer-of-trimers assembly, which we demonstrate is a result of the E484Q mutation and with unknown biological implications. The combination of increased antibody escape and enhanced ACE2 binding provides an explanation, in part, for the rapid global dominance of the Delta variant. | |||||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 181.5 KB | 表示 | ![]() |
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PDB形式 | ![]() | 132.1 KB | 表示 | ![]() |
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その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 810.2 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 810.9 KB | 表示 | |
XML形式データ | ![]() | 32.9 KB | 表示 | |
CIF形式データ | ![]() | 49.4 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 25856MC ![]() 7tewC ![]() 7texC ![]() 7teyC ![]() 7tf0C ![]() 7tf1C ![]() 7tf2C ![]() 7tf3C ![]() 7tf4C ![]() 7tf5C 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 ( |
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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: 142482.609 Da / 分子数: 1 / 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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#2: タンパク質 | 分子量: 70386.992 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() | ||
#3: 糖 | ChemComp-NAG / 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 |
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試料調製
構成要素 |
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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 |
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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: TFS 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): 3000 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.27 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 105037 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 115.49 Å2 | ||||||||||||||||||||||||
拘束条件 |
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