7F5G

The crystal structure of RBD-Nanobody complex, DL4 (SA4)

7F5G の概要

• エントリーDOI: 10.2210/pdb7f5g/pdb
• 分子名称: Spike glycoprotein, Nanobody DL4, alpha-L-fucopyranose-(1-3)-[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)
• 機能のキーワード: nanobody, rbd, neutralizing antibody, receptor-binding domain, sars-cov-2, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 83332.80

構造登録者

Li, T.,Lai, Y.,Zhou, Y.,Tan, J.,Li, D. (登録日: 2021-06-22, 公開日: 2022-05-25, 最終更新日: 2024-11-20)

主引用文献

Li, T.,Zhou, B.,Li, Y.,Huang, S.,Luo, Z.,Zhou, Y.,Lai, Y.,Gautam, A.,Bourgeau, S.,Wang, S.,Bao, J.,Tan, J.,Lavillette, D.,Li, D.
Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2.
Int.J.Biol.Macromol., 209:1379-1388, 2022

PubMed Abstract: SARS-CoV-2 engages with human cells through the binding of its Spike receptor-binding domain (S-RBD) to the receptor ACE2. Molecular blocking of this engagement represents a proven strategy to treat COVID-19. Here, we report a single-chain antibody (nanobody, DL4) isolated from immunized alpaca with picomolar affinity to RBD. DL4 neutralizes SARS-CoV-2 pseudoviruses with an IC of 0.101 μg mL (6.2 nM). A crystal structure of the DL4-RBD complex at 1.75-Å resolution unveils the interaction detail and reveals a direct competition mechanism for DL4's ACE2-blocking and hence neutralizing activity. The structural information allows us to rationally design a mutant with higher potency. Our work adds diversity of neutralizing nanobodies against SARS-CoV-2 and should encourage protein engineering to improve antibody affinities in general.

PubMed: 35460753
DOI: 10.1016/j.ijbiomac.2022.04.096

実験手法

X-RAY DIFFRACTION (1.75 Å)