登録情報 データベース : EMDB / ID : EMD-44727 ダウンロードとリンクタイトル SARS-CoV-2 spike HexaPro protein in complex with T18A trimeric antagonist マップデータ 詳細 試料複合体 : Complex of SARS-CoV-2 spike HexaPro protein with trimeric T18A antagonist複合体 : ACE2 domains of T18A antagonistタンパク質・ペプチド : Collagen alpha-1(XVIII) chain,Processed angiotensin-converting enzyme 2複合体 : SARS-CoV-2 spike HexaPro protein trimerタンパク質・ペプチド : Spike glycoproteinリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranose 詳細 キーワード trimeric antagonist SARS-CoV-2 complex / VIRAL PROTEIN-ANTAGONIST complex機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
response to hydrostatic pressure / Collagen chain trimerization / extracellular matrix structural constituent conferring tensile strength / Collagen biosynthesis and modifying enzymes / endothelial cell morphogenesis / Laminin interactions / collagen trimer / Assembly of collagen fibrils and other multimeric structures / Activation of Matrix Metalloproteinases / positive regulation of amino acid transport ... response to hydrostatic pressure / Collagen chain trimerization / extracellular matrix structural constituent conferring tensile strength / Collagen biosynthesis and modifying enzymes / endothelial cell morphogenesis / Laminin interactions / collagen trimer / Assembly of collagen fibrils and other multimeric structures / Activation of Matrix Metalloproteinases / positive regulation of amino acid transport / angiotensin-converting enzyme 2 / Collagen degradation / 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 / basement membrane / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / regulation of cardiac conduction / maternal process involved in female pregnancy / Integrin cell surface interactions / peptidyl-dipeptidase activity / regulation of vasoconstriction / transporter activator activity / Metabolism of Angiotensinogen to Angiotensins / carboxypeptidase activity / angiotensin maturation / viral life cycle / Attachment and Entry / receptor-mediated endocytosis of virus by host cell / metallocarboxypeptidase activity / visual perception / positive regulation of cardiac muscle contraction / regulation of cytokine production / blood vessel diameter maintenance / animal organ morphogenesis / skeletal system development / negative regulation of smooth muscle cell proliferation / brush border membrane / negative regulation of ERK1 and ERK2 cascade / positive regulation of reactive oxygen species metabolic process / metallopeptidase activity / endocytic vesicle membrane / regulation of cell population proliferation / : / virus receptor activity / regulation of inflammatory response / angiogenesis / symbiont-mediated disruption of host tissue / endopeptidase activity / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / viral translation / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / Potential therapeutics for SARS / structural constituent of virion / membrane fusion / entry receptor-mediated virion attachment to host cell / 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 / cell adhesion / host cell surface receptor binding / cilium / symbiont-mediated suppression of host innate immune response / apical plasma membrane / receptor ligand activity / membrane raft / endocytosis involved in viral entry into host cell / endoplasmic reticulum lumen / response to xenobiotic stimulus / negative regulation of cell population proliferation / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / cell surface / negative regulation of transcription by RNA polymerase II / extracellular space / extracellular exosome / extracellular region / zinc ion binding / metal ion binding / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 Domain of unknown function DUF959, collagen XVIII, N-terminal / Collagen alpha-1(XVIII) chain, frizzled domain / Domain of Unknown Function (DUF959) / Collagenase NC10/endostatin / Collagen type XV/XVIII, trimerization domain / Collagenase NC10 and Endostatin / Collagen trimerization domain / : / Thrombospondin N-terminal -like domains. / : ... Domain of unknown function DUF959, collagen XVIII, N-terminal / Collagen alpha-1(XVIII) chain, frizzled domain / Domain of Unknown Function (DUF959) / Collagenase NC10/endostatin / Collagen type XV/XVIII, trimerization domain / Collagenase NC10 and Endostatin / Collagen trimerization domain / : / Thrombospondin N-terminal -like domains. / : / Frizzled / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / Collagen triple helix repeat / Collagen triple helix repeat (20 copies) / C-type lectin-like/link domain superfamily / Collectrin domain / Renal amino acid transporter / Collectrin-like domain profile. / C-type lectin fold / Peptidase M2, peptidyl-dipeptidase A / Angiotensin-converting enzyme / Peptidase family M2 domain profile. / Neutral zinc metallopeptidases, zinc-binding region signature. / Concanavalin A-like lectin/glucanase domain superfamily / Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, N-terminal domain superfamily / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Spike glycoprotein, betacoronavirus / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 類似検索 - ドメイン・相同性 Spike glycoprotein / Collagen alpha-1(XVIII) chain / Angiotensin-converting enzyme 2 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Severe acute respiratory syndrome coronavirus 2 (ウイルス)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.73 Å 詳細 データ登録者Young T 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 Other private 米国
引用ジャーナル : Commun Biol / 年 : 2025タイトル : Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist.著者 : Juliet Gonzales / Tynan Young / Hyeran Choi / Miso Park / Yead Jewel / Chengcheng Fan / Rahul Purohit / Pamela J Bjorkman / John C Williams / 要旨 : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, utilizes membrane-bound, angiotensin-converting enzyme II (ACE2) for internalization and infection. ... Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, utilizes membrane-bound, angiotensin-converting enzyme II (ACE2) for internalization and infection. We describe the development of a biologic that takes advantage of the proximity of the N-terminus of bound ACE2 to the three-fold symmetry axis of the spike protein to create an ultrapotent, trivalent ACE2 entry antagonist. Distinct disulfide bonds were added to enhance serum stability and a single point mutation was introduced to eliminate enzymatic activity. Through surface plasmon resonance, pseudovirus neutralization assays, and single-particle cryo-electron microscopy, we show this antagonist binds to and inhibits SARS-CoV-2 variants. We further show the antagonist binds to and inhibits a 2003 SARS-CoV-1 strain. Collectively, structural insight has allowed us to design a universal trivalent antagonist against all variants of SARS-CoV-2 tested, suggesting it will be active against the emergence of future mutants. 履歴 登録 2024年5月2日 - ヘッダ(付随情報) 公開 2025年8月27日 - マップ公開 2025年8月27日 - 更新 2025年10月29日 - 現状 2025年10月29日 処理サイト : RCSB / 状態 : 公開
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