7KKJ

Structure of anti-SARS-CoV-2 Spike nanobody mNb6

7KKJ の概要

• エントリーDOI: 10.2210/pdb7kkj/pdb
• 分子名称: Synthetic nanobody mNb6, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: complex, nanobody, vhh, immune system
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27701.95

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: 2020-11-25, 最終更新日: 2024-10-30)

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.,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

X-RAY DIFFRACTION (2.05 Å)