7wri
From Proteopedia
Cryo-EM structure of SARS-CoV-2 Omicron spike receptor-binding domain in complex with mouse ACE2
Structural highlights
FunctionACE2_MOUSE 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 (By similarity). By cleavage of angiotensin II, may be an important regulator of heart function (PubMed:12075344, PubMed:12967627). By cleavage of angiotensin II, may also have a protective role in acute lung injury (PubMed:16001071). Plays an important role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19, regulating its trafficking on the cell surface and its activity (PubMed:19185582, PubMed:18424768, PubMed:22677001).[UniProtKB:Q9BYF1][1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe Omicron variant of SARS-CoV-2 carries multiple unusual mutations, particularly in the receptor-binding domain (RBD) of the spike (S) protein. Moreover, host-adapting mutations, such as residues 493, 498, and 501, were also observed in the Omicron RBD, which indicates that it is necessary to evaluate the interspecies transmission risk of the Omicron variant. Herein, we evaluated the interspecies recognition of the Omicron BA.1 and Delta RBDs by 27 ACE2 orthologs, including humans. We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet, rodents, more bats (least horseshoe bat and greater horseshoe bat) and lesser hedgehog tenrec. Additionally, we determined the cryo-electron microscopy (cryo-EM) structure of the Omicron BA.1 S protein complexed with mouse ACE2 (mACE2) and the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2). Several key residues for the host range have been identified. These results suggest that surveillance should be enhanced on the Omicron variant for its broader-species receptor binding to prevent spillover and expansion of reservoir hosts for a prolonged pandemic. Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s.,Li L, Han P, Huang B, Xie Y, Li W, Zhang D, Han P, Xu Z, Bai B, Zhou J, Kang X, Li X, Zheng A, Zhang R, Qiao S, Zhao X, Qi J, Wang Q, Liu K, Gao GF Cell Discov. 2022 Jul 12;8(1):65. doi: 10.1038/s41421-022-00431-0. PMID:35821014[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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