7KKL
SARS-CoV-2 Spike in complex with neutralizing nanobody mNb6
Summary for 7KKL
| Entry DOI | 10.2210/pdb7kkl/pdb |
| EMDB information | 22907 22908 22909 22910 22911 |
| Descriptor | 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) |
| Functional Keywords | complex, nanobody, vhh, viral protein-immune system complex, viral protein/immune system |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) More |
| Total number of polymer chains | 6 |
| Total formula weight | 481733.33 |
| Authors | 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 (deposition date: 2020-10-27, release date: 2020-11-11, Last modification date: 2024-10-16) |
| Primary citation | 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 Cited by 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: 33154106DOI: 10.1126/science.abe3255 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.85 Å) |
Structure validation
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