7c8d | pdb_00007c8d
Cryo-EM structure of cat ACE2 and SARS-CoV-2 RBD
Structural highlights
FunctionACE2_FELCA Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II. Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin. Also cleaves other biological peptides, such as apelins, casomorphins and dynorphin A. Plays an important role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19 in intestine, regulating trafficking, expression on the cell surface, and its catalytic activity.[UniProtKB:Q9BYF1] Publication Abstract from PubMedSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the recent pandemic COVID-19, is reported to have originated from bats, with its intermediate host unknown to date. Here, we screened 26 animal counterparts of the human ACE2 (hACE2), the receptor for SARS-CoV-2 and SARS-CoV, and found that the ACE2s from various species, including pets, domestic animals and multiple wild animals, could bind to SARS-CoV-2 receptor binding domain (RBD) and facilitate the transduction of SARS-CoV-2 pseudovirus. Comparing to SARS-CoV-2, SARS-CoV seems to have a slightly wider range in choosing its receptor. We further resolved the cryo-electron microscopy (cryo-EM) structure of the cat ACE2 (cACE2) in complex with the SARS-CoV-2 RBD at a resolution of 3 A, revealing similar binding mode as hACE2 to the SARS-CoV-2 RBD. These results shed light on pursuing the intermediate host of SARS-CoV-2 and highlight the necessity of monitoring susceptible hosts to prevent further outbreaks. Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2.,Wu L, Chen Q, Liu K, Wang J, Han P, Zhang Y, Hu Y, Meng Y, Pan X, Qiao C, Tian S, Du P, Song H, Shi W, Qi J, Wang HW, Yan J, Gao GF, Wang Q Cell Discov. 2020 Sep 29;6:68. doi: 10.1038/s41421-020-00210-9. eCollection 2020. PMID:33020722[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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