7D30

Structure of sybody MR17-SR31 fusion in complex with the SARS-CoV-2 S Receptor Binding domain (RBD)

Summary for 7D30

• Entry DOI: 10.2210/pdb7d30/pdb
• Descriptor: sybody fusion of MR17-SR31 with a GS linker, Spike protein S1, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)][alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: coronavirus, covid-19, nanobody, neutralizing antibody, receptor binding protein, sars-cov-2, s protein, synthetic antibody, vhh., protein binding
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 60133.98

Authors

Li, T.,Yao, H.,Cai, H.,Qin, W.,Li, D. (deposition date: 2020-09-17, release date: 2021-02-17, Last modification date: 2024-10-09)

Primary citation

Yao, H.,Cai, H.,Li, T.,Zhou, B.,Qin, W.,Lavillette, D.,Li, D.
A high-affinity RBD-targeting nanobody improves fusion partner's potency against SARS-CoV-2.
Plos Pathog., 17:e1009328-e1009328, 2021

PubMed Abstract: A key step to the SARS-CoV-2 infection is the attachment of its Spike receptor-binding domain (S RBD) to the host receptor ACE2. Considerable research has been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. Simple and effective strategies to increase potency are desirable for such studies when antibodies are only modestly effective. Here, we identify and characterize a high-affinity synthetic nanobody (sybody, SR31) as a fusion partner to improve the potency of RBM-antibodies. Crystallographic studies reveal that SR31 binds to RBD at a conserved and 'greasy' site distal to RBM. Although SR31 distorts RBD at the interface, it does not perturb the RBM conformation, hence displaying no neutralizing activities itself. However, fusing SR31 to two modestly neutralizing sybodies dramatically increases their affinity for RBD and neutralization activity against SARS-CoV-2 pseudovirus. Our work presents a tool protein and an efficient strategy to improve nanobody potency.

PubMed: 33657135
DOI: 10.1371/journal.ppat.1009328

Experimental method

X-RAY DIFFRACTION (2.1 Å)