7A25

Cryo-EM structure of the SARS-CoV-2 spike protein bound to neutralizing sybodies (Sb23)

7A25 の概要

• エントリーDOI: 10.2210/pdb7a25/pdb
• EMDBエントリー: 11616
• 分子名称: Spike glycoprotein, Sybody 23, 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, complex, nanobody, spike, 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: 431465.25

構造登録者

Hallberg, B.M.,Das, H. (登録日: 2020-08-16, 公開日: 2020-11-25, 最終更新日: 2024-11-20)

主引用文献

Custodio, T.F.,Das, H.,Sheward, D.J.,Hanke, L.,Pazicky, S.,Pieprzyk, J.,Sorgenfrei, M.,Schroer, M.A.,Gruzinov, A.Y.,Jeffries, C.M.,Graewert, M.A.,Svergun, D.I.,Dobrev, N.,Remans, K.,Seeger, M.A.,McInerney, G.M.,Murrell, B.,Hallberg, B.M.,Low, C.
Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2.
Nat Commun, 11:5588-5588, 2020

PubMed Abstract: The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Therapeutic neutralizing antibodies constitute a key short-to-medium term approach to tackle COVID-19. However, traditional antibody production is hampered by long development times and costly production. Here, we report the rapid isolation and characterization of nanobodies from a synthetic library, known as sybodies (Sb), that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Several binders with low nanomolar affinities and efficient neutralization activity were identified of which Sb23 displayed high affinity and neutralized pseudovirus with an IC of 0.6 µg/ml. A cryo-EM structure of the spike bound to Sb23 showed that Sb23 binds competitively in the ACE2 binding site. Furthermore, the cryo-EM reconstruction revealed an unusual conformation of the spike where two RBDs are in the 'up' ACE2-binding conformation. The combined approach represents an alternative, fast workflow to select binders with neutralizing activity against newly emerging viruses.

PubMed: 33149112
DOI: 10.1038/s41467-020-19204-y

実験手法

ELECTRON MICROSCOPY (3.06 Å)