7FDG

SARS-COV-2 Spike RBDMACSp6 binding to hACE2

Summary for 7FDG

• Entry DOI: 10.2210/pdb7fdg/pdb
• EMDB information: 31542
• Descriptor: Angiotensin-converting enzyme 2, Spike protein S1, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sars-cov-2 spike, mouse-adapted, rbd, ace2, virus protein, virus, viral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 97035.93

Authors

Wang, X.,Cao, L. (deposition date: 2021-07-16, release date: 2021-08-25, Last modification date: 2024-10-09)

Primary citation

Sun, S.,Gu, H.,Cao, L.,Chen, Q.,Ye, Q.,Yang, G.,Li, R.T.,Fan, H.,Deng, Y.Q.,Song, X.,Qi, Y.,Li, M.,Lan, J.,Feng, R.,Guo, Y.,Zhu, N.,Qin, S.,Wang, L.,Zhang, Y.F.,Zhou, C.,Zhao, L.,Chen, Y.,Shen, M.,Cui, Y.,Yang, X.,Wang, X.,Tan, W.,Wang, H.,Wang, X.,Qin, C.F.
Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2.
Nat Commun, 12:5654-5654, 2021

PubMed Abstract: There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution.

PubMed: 34580297
DOI: 10.1038/s41467-021-25903-x

Experimental method

ELECTRON MICROSCOPY (3.69 Å)