6ZH9

Ternary complex CR3022 H11-H4 and RBD (SARS-CoV-2)

This is a non-PDB format compatible entry.

Summary for 6ZH9

• Entry DOI: 10.2210/pdb6zh9/pdb
• Descriptor: CR3022 heavy, CR3022 Light chain, Spike glycoprotein, ... (4 entities in total)
• Functional Keywords: covid19, nanobody, sars-cov-2, antiviral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 84223.11

Authors

Naismith, J.H.,Mikolajek, H.,Le Bas, A. (deposition date: 2020-06-21, release date: 2020-09-02, Last modification date: 2024-01-24)

Primary citation

Huo, J.,Le Bas, A.,Ruza, R.R.,Duyvesteyn, H.M.E.,Mikolajek, H.,Malinauskas, T.,Tan, T.K.,Rijal, P.,Dumoux, M.,Ward, P.N.,Ren, J.,Zhou, D.,Harrison, P.J.,Weckener, M.,Clare, D.K.,Vogirala, V.K.,Radecke, J.,Moynie, L.,Zhao, Y.,Gilbert-Jaramillo, J.,Knight, M.L.,Tree, J.A.,Buttigieg, K.R.,Coombes, N.,Elmore, M.J.,Carroll, M.W.,Carrique, L.,Shah, P.N.M.,James, W.,Townsend, A.R.,Stuart, D.I.,Owens, R.J.,Naismith, J.H.
Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2.
Nat.Struct.Mol.Biol., 27:846-854, 2020

PubMed Abstract: The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (K of 39 and 12 nM, respectively) and block its interaction with ACE2. Single-particle cryo-EM revealed that both nanobodies bind to all three RBDs in the spike trimer. Crystal structures of each nanobody-RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD-ACE2 interaction. Nanobody-Fc fusions showed neutralizing activity against SARS-CoV-2 (4-6 nM for H11-H4, 18 nM for H11-D4) and additive neutralization with the SARS-CoV-1/2 antibody CR3022.

PubMed: 32661423
DOI: 10.1038/s41594-020-0469-6

Experimental method

X-RAY DIFFRACTION (3.31 Å)