7yeg | pdb_00007yeg

SARS-CoV-2 Spike (6P) in complex with 3 R1-32 Fabs and 3 ACE2

spinqualitylabelsall models 7yeg, resolution 3.73Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yeg is a 12 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAG, ZN 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 Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis of epitope location, neutralization mechanism and analysis of antibody binding to spike variants, we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of the identified population antibody response. These substitutions, including L452R (present in the Delta variant), disrupt interactions mediated by the VH1-69-specific hydrophobic HCDR2 to impair antibody-antigen association, enabling variants to escape. The first Omicron variants were sensitive to antibody R1-32 but subvariants that harbour L452R quickly emerged and spread. Our results provide insights into how SARS-CoV-2 variants emerge and evade host immune responses. SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope.,He P, Liu B, Gao X, Yan Q, Pei R, Sun J, Chen Q, Hou R, Li Z, Zhang Y, Zhao J, Sun H, Feng B, Wang Q, Yi H, Hu P, Li P, Zhang Y, Chen Z, Niu X, Zhong X, Jin L, Liu X, Qu K, Ciazynska KA, Carter AP, Briggs JAG, Chen J, Liu J, Chen X, He J, Chen L, Xiong X Nat Microbiol. 2022 Oct;7(10):1635-1649. doi: 10.1038/s41564-022-01235-4. Epub , 2022 Sep 23. PMID:36151403 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Angiotensin-Converting Enzyme 3D structures

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