8h06
From Proteopedia
Cryo-EM structure of SARS-CoV-2 Omicron BA.4/5 RBD in complex with human ACE2 (local refinement)
Structural highlights
FunctionACE2_HUMAN Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.[1] [2] [3] Publication Abstract from PubMedMultiple SARS-CoV-2 Omicron sub-variants, such as BA.2, BA.2.12.1, BA.4, and BA.5, emerge one after another. BA.5 has become the dominant strain worldwide. Additionally, BA.2.75 is significantly increasing in some countries. Exploring their receptor binding and interspecies transmission risk is urgently needed. Herein, we examine the binding capacities of human and other 28 animal ACE2 orthologs covering nine orders towards S proteins of these sub-variants. The binding affinities between hACE2 and these sub-variants remain in the range as that of previous variants of concerns (VOCs) or interests (VOIs). Notably, R493Q reverse mutation enhances the bindings towards ACE2s from humans and many animals closely related to human life, suggesting an increased risk of cross-species transmission. Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition. Structural basis for receptor binding and broader interspecies receptor recognition of currently circulating Omicron sub-variants.,Zhao Z, Xie Y, Bai B, Luo C, Zhou J, Li W, Meng Y, Li L, Li D, Li X, Li X, Wang X, Sun J, Xu Z, Sun Y, Zhang W, Fan Z, Zhao X, Wu L, Ma J, Li OY, Shang G, Chai Y, Liu K, Wang P, Gao GF, Qi J Nat Commun. 2023 Jul 21;14(1):4405. doi: 10.1038/s41467-023-39942-z. PMID:37479708[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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