7FC3

structure of NL63 receptor-binding domain complexed with horse ACE2

Summary for 7FC3

• Entry DOI: 10.2210/pdb7fc3/pdb
• Descriptor: Spike protein S1, Angiotensin-converting enzyme, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: nl63, receptor-binding domain, horse ace2, viral protein, viral protein-protein binding complex, viral protein/protein binding
• Biological source: Human coronavirus NL63 (HCoV-NL63); More
• Total number of polymer chains: 2
• Total formula weight: 84463.71

Authors

Wang, X.Q.,Ge, J.W.,Lan, J. (deposition date: 2021-07-13, release date: 2021-09-22, Last modification date: 2024-11-06)

Primary citation

Lan, J.,Chen, P.,Liu, W.,Ren, W.,Zhang, L.,Ding, Q.,Zhang, Q.,Wang, X.,Ge, J.
Structural insights into the binding of SARS-CoV-2, SARS-CoV, and hCoV-NL63 spike receptor-binding domain to horse ACE2.
Structure, 30:1432-1442.e4, 2022

PubMed Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and human coronavirus (hCoV)-NL63 utilize ACE2 as the functional receptor for cell entry, which leads to zoonotic infection. Horses (Equus caballus) attracted our attention because the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 and SARS-CoV-2-related coronaviruses bind equine ACE2 (eACE2) with high affinity. Here we show that eACE2 binds the RBDs of these three coronaviruses and also SARS-CoV-2 variants but with lower affinities compared with human ACE2 (hACE2). Structural analysis and mutation assays indicated that eACE2-H41 accounts for the lower binding affinity of eACE2 to the RBDs of SARS-CoV-2 variants (Alpha, Beta, and Gamma), SARS-CoV, and hCoV-NL63. Pseudovirus infection assays showed that the SARS-CoV-2 Delta strain (B.1.617.2) displayed a significantly increased infection efficiency in eACE2-expressing HeLa cells. Our results reveal the molecular basis of eACE2 binding to the RBDs of SARS-CoV, SARS-CoV-2, and hCoV-NL63, which provides insights into the potential animal transmission of these ACE2-dependent coronaviruses.

PubMed: 35917815
DOI: 10.1016/j.str.2022.07.005

Experimental method

X-RAY DIFFRACTION (3.19 Å)