6ZXN

Cryo-EM structure of the SARS-CoV-2 spike protein bound to neutralizing nanobodies (Ty1)

6ZXN の概要

• エントリーDOI: 10.2210/pdb6zxn/pdb
• EMDBエントリー: 11526
• 分子名称: Spike glycoprotein, Nanobody Ty1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, spike protein, neutralising antibody, 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: 6
• 化学式量合計: 483838.82

構造登録者

Hallberg, B.M.,Das, H. (登録日: 2020-07-30, 公開日: 2020-09-23, 最終更新日: 2024-10-23)

主引用文献

Hanke, L.,Vidakovics Perez, L.,Sheward, D.J.,Das, H.,Schulte, T.,Moliner-Morro, A.,Corcoran, M.,Achour, A.,Karlsson Hedestam, G.B.,Hallberg, B.M.,Murrell, B.,McInerney, G.M.
An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction.
Nat Commun, 11:4420-4420, 2020

PubMed Abstract: SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. Ty1 binds the RBD with high affinity, occluding ACE2. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the 'up' and 'down' conformations, sterically hindering RBD-ACE2 binding. While fusion to an Fc domain renders Ty1 extremely potent, Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody, which can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Ty1 is therefore an excellent candidate as an intervention against COVID-19.

PubMed: 32887876
DOI: 10.1038/s41467-020-18174-5

実験手法

ELECTRON MICROSCOPY (2.93 Å)