7F5H

The crystal structure of RBD-Nanobody complex, DL28 (SC4)

Summary for 7F5H

• Entry DOI: 10.2210/pdb7f5h/pdb
• Descriptor: SARS-CoV-2 Spike Receptor-Binding Domain (RBD), Nanobody DL28, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: nanobody, rbd, neutralizing antibody, sars-cov-2, receptor-binding domain, receptor-binding motif, rbm distortion, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 4
• Total formula weight: 80475.59

Authors

Luo, Z.P.,Li, T.,Lai, Y.,Zhou, Y.,Tan, J.,Li, D. (deposition date: 2021-06-22, release date: 2022-06-29, Last modification date: 2024-10-16)

Primary citation

Li, T.,Zhou, B.,Luo, Z.,Lai, Y.,Huang, S.,Zhou, Y.,Li, Y.,Gautam, A.,Bourgeau, S.,Wang, S.,Bao, J.,Tan, J.,Lavillette, D.,Li, D.
Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants.
Front Microbiol, 13:875840-875840, 2022

PubMed Abstract: SARS-CoV-2 and its variants, such as the Omicron continue to threaten public health. The virus recognizes the host cell by attaching its Spike (S) receptor-binding domain (RBD) to the host receptor, ACE2. Therefore, RBD is a primary target for neutralizing antibodies and vaccines. Here, we report the isolation and biological and structural characterization of a single-chain antibody (nanobody) from RBD-immunized alpaca. The nanobody, named DL28, binds to RBD tightly with a of 1.56 nM and neutralizes the original SARS-CoV-2 strain with an IC of 0.41 μg mL. Neutralization assays with a panel of variants of concern (VOCs) reveal its wide-spectrum activity with IC values ranging from 0.35 to 1.66 μg mL for the Alpha/Beta/Gamma/Delta and an IC of 0.66 μg mL for the currently prevalent Omicron. Competition binding assays show that DL28 blocks ACE2-binding. However, structural characterizations and mutagenesis suggest that unlike most antibodies, the blockage by DL28 does not involve direct competition or steric hindrance. Rather, DL28 may use a "conformation competition" mechanism where it excludes ACE2 by keeping an RBD loop in a conformation incompatible with ACE2-binding.

PubMed: 35722331
DOI: 10.3389/fmicb.2022.875840

Experimental method

X-RAY DIFFRACTION (3 Å)