7KKJ

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

Summary for 7KKJ

• Entry DOI: 10.2210/pdb7kkj/pdb
• Descriptor: Synthetic nanobody mNb6, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: complex, nanobody, vhh, immune system
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 27701.95

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: 2020-11-25, Last modification date: 2024-10-30)

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.,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

Experimental method

X-RAY DIFFRACTION (2.05 Å)