- EMDB-11980: SARS-CoV-spike RBD bound to two neutralising nanobodies. -
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基本情報
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データベース: EMDB / ID: EMD-11980
タイトル
SARS-CoV-spike RBD bound to two neutralising nanobodies.
マップデータ
Resolve Cryo-EM in the PHENIX suite used on the half-maps from localised reconstruction.
試料
複合体: Structure of SARS-CoV-2 spike RBD in complex with SARS-CoV-2 neutralizing biparatopic nanobody VE
複合体: Spike glycoprotein
タンパク質・ペプチド: Spike protein S1
複合体: biparatopic nanobody VE
タンパク質・ペプチド: SARS-CoV-2 neutralizing biparatopic nanobody VE,nanobody E from Lama glama,SARS-CoV-2 neutralizing biparatopic nanobody VE,nanobody E from Lama glama
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
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 / 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
ジャーナル: Science / 年: 2021 タイトル: Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape. 著者: Paul-Albert Koenig / Hrishikesh Das / Hejun Liu / Beate M Kümmerer / Florian N Gohr / Lea-Marie Jenster / Lisa D J Schiffelers / Yonas M Tesfamariam / Miki Uchima / Jennifer D Wuerth / Karl ...著者: Paul-Albert Koenig / Hrishikesh Das / Hejun Liu / Beate M Kümmerer / Florian N Gohr / Lea-Marie Jenster / Lisa D J Schiffelers / Yonas M Tesfamariam / Miki Uchima / Jennifer D Wuerth / Karl Gatterdam / Natalia Ruetalo / Maria H Christensen / Caroline I Fandrey / Sabine Normann / Jan M P Tödtmann / Steffen Pritzl / Leo Hanke / Jannik Boos / Meng Yuan / Xueyong Zhu / Jonathan L Schmid-Burgk / Hiroki Kato / Michael Schindler / Ian A Wilson / Matthias Geyer / Kerstin U Ludwig / B Martin Hällberg / Nicholas C Wu / Florian I Schmidt / 要旨: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread, with devastating consequences. For passive immunization efforts, nanobodies have size and cost ...The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread, with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. In this study, we generated four neutralizing nanobodies that target the receptor binding domain of the SARS-CoV-2 spike protein. We used x-ray crystallography and cryo-electron microscopy to define two distinct binding epitopes. On the basis of these structures, we engineered multivalent nanobodies with more than 100 times the neutralizing activity of monovalent nanobodies. Biparatopic nanobody fusions suppressed the emergence of escape mutants. Several nanobody constructs neutralized through receptor binding competition, whereas other monovalent and biparatopic nanobodies triggered aberrant activation of the spike fusion machinery. These premature conformational changes in the spike protein forestalled productive fusion and rendered the virions noninfectious.
全体 : Structure of SARS-CoV-2 spike RBD in complex with SARS-CoV-2 neut...
全体
名称: Structure of SARS-CoV-2 spike RBD in complex with SARS-CoV-2 neutralizing biparatopic nanobody VE
要素
複合体: Structure of SARS-CoV-2 spike RBD in complex with SARS-CoV-2 neutralizing biparatopic nanobody VE
複合体: Spike glycoprotein
タンパク質・ペプチド: Spike protein S1
複合体: biparatopic nanobody VE
タンパク質・ペプチド: SARS-CoV-2 neutralizing biparatopic nanobody VE,nanobody E from Lama glama,SARS-CoV-2 neutralizing biparatopic nanobody VE,nanobody E from Lama glama
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
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超分子 #1: Structure of SARS-CoV-2 spike RBD in complex with SARS-CoV-2 neut...
超分子
名称: Structure of SARS-CoV-2 spike RBD in complex with SARS-CoV-2 neutralizing biparatopic nanobody VE タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 詳細: Density from localised reconstruction from full spike - VE data.
分子 #2: SARS-CoV-2 neutralizing biparatopic nanobody VE,nanobody E from L...
分子
名称: SARS-CoV-2 neutralizing biparatopic nanobody VE,nanobody E from Lama glama,SARS-CoV-2 neutralizing biparatopic nanobody VE,nanobody E from Lama glama タイプ: protein_or_peptide / ID: 2 詳細: Nanobody V from Vicugna pacos and nanobody E from Lama glama connected with a 15 residue linker,Nanobody V from Vicugna pacos and nanobody E from Lama glama connected with a 15 residue ...詳細: Nanobody V from Vicugna pacos and nanobody E from Lama glama connected with a 15 residue linker,Nanobody V from Vicugna pacos and nanobody E from Lama glama connected with a 15 residue linker, 1-119 nanobody from Alpacka, 120-136: linker, 137-263: nanobody from Llama, 264-283: cloning and purification tag,Nanobody V from Vicugna pacos and nanobody E from Lama glama connected with a 15 residue linker,Nanobody V from Vicugna pacos and nanobody E from Lama glama connected with a 15 residue linker, 1-119 nanobody from Alpacka, 120-136: linker, 137-263: nanobody from Llama, 264-283: cloning and purification tag コピー数: 1 / 光学異性体: LEVO