8WLR

Cryo-EM structure of SARS-CoV-2 prototype spike protein receptor-binding domain in complex with hippopotamus ACE2

Summary for 8WLR

• Entry DOI: 10.2210/pdb8wlr/pdb
• EMDB information: 37629
• Descriptor: Angiotensin-converting enzyme, Spike glycoprotein, ZINC ION, ... (4 entities in total)
• Functional Keywords: complex, viral protein/hydrolase, viral protein-hydrolase complex
• Biological source: Hippopotamus amphibius; More
• Total number of polymer chains: 2
• Total formula weight: 204741.37

Authors

Han, P.,Yang, R.R.,Li, S.H. (deposition date: 2023-09-30, release date: 2024-03-27, Last modification date: 2025-07-16)

Primary citation

Yang, R.,Han, P.,Han, P.,Li, D.,Zhao, R.,Niu, S.,Liu, K.,Li, S.,Tian, W.X.,Gao, G.F.
Molecular basis of hippopotamus ACE2 binding to SARS-CoV-2.
J.Virol., 98:e0045124-e0045124, 2024

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a wide range of hosts, including hippopotami, which are semi-aquatic mammals and phylogenetically closely related to Cetacea. In this study, we characterized the binding properties of hippopotamus angiotensin-converting enzyme 2 (hiACE2) to the spike (S) protein receptor binding domains (RBDs) of the SARS-CoV-2 prototype (PT) and variants of concern (VOCs). Furthermore, the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 PT S protein complexed with hiACE2 was resolved. Structural and mutational analyses revealed that L30 and F83, which are specific to hiACE2, played a crucial role in the hiACE2/SARS-CoV-2 RBD interaction. In addition, comparative and structural analysis of ACE2 orthologs suggested that the cetaceans may have the potential to be infected by SARS-CoV-2. These results provide crucial molecular insights into the susceptibility of hippopotami to SARS-CoV-2 and suggest the potential risk of SARS-CoV-2 VOCs spillover and the necessity for surveillance.

PubMed: 38591877
DOI: 10.1128/jvi.00451-24

Experimental method

ELECTRON MICROSCOPY (3.12 Å)