7D30

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

7D30 の概要

• エントリーDOI: 10.2210/pdb7d30/pdb
• 分子名称: 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)
• 機能のキーワード: coronavirus, covid-19, nanobody, neutralizing antibody, receptor binding protein, sars-cov-2, s protein, synthetic antibody, vhh., protein binding
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60133.98

構造登録者

Li, T.,Yao, H.,Cai, H.,Qin, W.,Li, D. (登録日: 2020-09-17, 公開日: 2021-02-17, 最終更新日: 2024-10-09)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.1 Å)