9jj6

BtHKU5-CoV-2-441 Spike RBD domain binding to hACE2

spinqualitylabelsall models 9jj6, resolution 2.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9jj6 is a 2 chain structure with sequence from Homo sapiens and Pipistrellus bat coronavirus HKU5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.94Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACE2_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. Publication Abstract from PubMed Merbecoviruses comprise four viral species with remarkable genetic diversity: MERS-related coronavirus, Tylonycterisbat coronavirus HKU4, Pipistrellusbat coronavirus HKU5, and Hedgehog coronavirus 1. However, the potential human spillover risk of animal merbecoviruses remains to be investigated. Here, we reported the discovery of HKU5-CoV lineage 2 (HKU5-CoV-2) in bats that efficiently utilize human angiotensin-converting enzyme 2 (ACE2) as a functional receptor and exhibits a broad host tropism. Cryo-EM analysis of HKU5-CoV-2 receptor-binding domain (RBD) and human ACE2 complex revealed an entirely distinct binding mode compared with other ACE2-utilizing merbecoviruses with RBD footprint largely shared with ACE2-using sarbecoviruses and NL63. Structural and functional analyses indicate that HKU5-CoV-2 has a better adaptation to human ACE2 than lineage 1 HKU5-CoV. Authentic HKU5-CoV-2 infected human ACE2-expressing cell lines and human respiratory and enteric organoids. This study reveals a distinct lineage of HKU5-CoVs in bats that efficiently use human ACE2 and underscores their potential zoonotic risk. Bat-infecting merbecovirus HKU5-CoV lineage 2 can use human ACE2 as a cell entry receptor.,Chen J, Zhang W, Li Y, Liu C, Dong T, Chen H, Wu C, Su J, Li B, Zhang W, Hu B, Jia J, Ma CB, Zhu Y, He X, Li A, Pan K, Lin H, Guo Z, Li C, Zhang L, Yan H, Zhou P, Peng W, Shi ZL Cell. 2025 Feb 12:S0092-8674(25)00144-8. doi: 10.1016/j.cell.2025.01.042. PMID:39970913 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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