7KKL

SARS-CoV-2 Spike in complex with neutralizing nanobody mNb6

7KKL の概要

• エントリーDOI: 10.2210/pdb7kkl/pdb
• EMDBエントリー: 22907 22908 22909 22910 22911
• 分子名称: Spike glycoprotein, Synthetic nanobody mNb6, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: complex, nanobody, vhh, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 481733.33

構造登録者

Schoof, M.S.,Faust, B.F.,Saunders, R.A.,Sangwan, S.,Rezelj, V.,Hoppe, N.,Boone, M.,Billesboelle, C.B.,Puchades, C.,Azumaya, C.M.,Kratochvil, H.T.,Zimanyi, M.,Desphande, I.,Liang, J.,Dickinson, S.,Nguyen, H.C.,Chio, C.M.,Merz, G.E.,Thompson, M.C.,Diwanji, D.,Schaefer, K.,Anand, A.A.,Dobzinski, N.,Zha, B.S.,Simoneau, C.R.,Leon, K.,White, K.M.,Chio, U.S.,Gupta, M.,Jin, M.,Li, F.,Liu, Y.,Zhang, K.,Bulkley, D.,Sun, M.,Smith, A.M.,Rizo, A.N.,Moss, F.,Brilot, A.F.,Pourmal, S.,Trenker, R.,Pospiech, T.,Gupta, S.,Barsi-Rhyne, B.,Belyy, V.,Barile-Hill, A.W.,Nock, S.,Liu, Y.,Krogan, N.J.,Ralston, C.Y.,Swaney, D.L.,Garcia-Sastre, A.,Ott, M.,Vignuzzi, M.,Walter, P.,Manglik, A.,QCRG Structural Biology Consortium (登録日: 2020-10-27, 公開日: 2020-11-11, 最終更新日: 2024-10-16)

主引用文献

Schoof, M.,Faust, B.,Saunders, R.A.,Sangwan, S.,Rezelj, V.,Hoppe, N.,Boone, M.,Billesbolle, C.B.,Puchades, C.,Azumaya, C.M.,Kratochvil, H.T.,Zimanyi, M.,Deshpande, I.,Liang, J.,Dickinson, S.,Nguyen, H.C.,Chio, C.M.,Merz, G.E.,Thompson, M.C.,Diwanji, D.,Schaefer, K.,Anand, A.A.,Dobzinski, N.,Zha, B.S.,Simoneau, C.R.,Leon, K.,White, K.M.,Chio, U.S.,Gupta, M.,Jin, M.,Li, F.,Liu, Y.,Zhang, K.,Bulkley, D.,Sun, M.,Smith, A.M.,Rizo, A.N.,Moss, F.,Brilot, A.F.,Pourmal, S.,Trenker, R.,Pospiech, T.,Gupta, S.,Barsi-Rhyne, B.,Belyy, V.,Barile-Hill, A.W.,Nock, S.,Liu, Y.,Krogan, N.J.,Ralston, C.Y.,Swaney, D.L.,Garcia-Sastre, A.,Ott, M.,Vignuzzi, M.,QCRG Structural Biology Consortium,Walter, P.,Manglik, A.
An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.
Science, 370:1473-1479, 2020

PubMed Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.

PubMed: 33154106
DOI: 10.1126/science.abe3255

実験手法

ELECTRON MICROSCOPY (2.85 Å)