7KJ4

SARS-CoV-2 Spike Glycoprotein with three ACE2 Bound

Summary for 7KJ4

• Entry DOI: 10.2210/pdb7kj4/pdb
• EMDB information: 22893
• Descriptor: Spike glycoprotein, Angiotensin-converting enzyme 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: viral protein, viral protein-hydrolase complex, viral protein/hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 6
• Total formula weight: 642230.31

Authors

Zhang, J.,Xiao, T.S.,Cai, Y.F.,Chen, B. (deposition date: 2020-10-25, release date: 2020-11-11, Last modification date: 2024-10-09)

Primary citation

Xiao, T.,Lu, J.,Zhang, J.,Johnson, R.I.,McKay, L.G.A.,Storm, N.,Lavine, C.L.,Peng, H.,Cai, Y.,Rits-Volloch, S.,Lu, S.,Quinlan, B.D.,Farzan, M.,Seaman, M.S.,Griffiths, A.,Chen, B.
A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent.
Nat.Struct.Mol.Biol., 28:202-209, 2021

PubMed Abstract: Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves as the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 is also a key negative regulator of the renin-angiotensin system that modulates vascular functions. We report here the properties of a trimeric ACE2 ectodomain variant, engineered using a structure-based approach. The trimeric ACE2 variant has a binding affinity of ~60 pM for the spike protein of SARS‑CoV‑2 (compared with 77 nM for monomeric ACE2 and 12-22 nM for dimeric ACE2 constructs), and its peptidase activity and the ability to block activation of angiotensin II receptor type 1 in the renin-angiotensin system are preserved. Moreover, the engineered ACE2 potently inhibits SARS‑CoV‑2 infection in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.

PubMed: 33432247
DOI: 10.1038/s41594-020-00549-3

Experimental method

ELECTRON MICROSCOPY (3.4 Å)