| Structural highlights
7sn0 is a 4 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.
| | Method: | X-ray diffraction, Resolution 3.08Å |
| Ligands: | BMA, CL, GAL, MAN, 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.[1] [2] [3]
Publication Abstract from PubMed
Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.
Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.,Nabel KG, Clark SA, Shankar S, Pan J, Clark LE, Yang P, Coscia A, McKay LGA, Varnum HH, Brusic V, Tolan NV, Zhou G, Desjardins M, Turbett SE, Kanjilal S, Sherman AC, Dighe A, LaRocque RC, Ryan ET, Tylek C, Cohen-Solal JF, Darcy AT, Tavella D, Clabbers A, Fan Y, Griffiths A, Correia IR, Seagal J, Baden LR, Charles RC, Abraham J Science. 2022 Jan 21;375(6578):eabl6251. doi: 10.1126/science.abl6251. Epub 2022 , Jan 21. PMID:34855508[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. PMID:10969042
- ↑ Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000 Oct 27;275(43):33238-43. PMID:10924499 doi:https://dx.doi.org/10.1074/jbc.M002615200
- ↑ Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27;426(6965):450-4. PMID:14647384 doi:https://dx.doi.org/10.1038/nature02145
- ↑ Nabel KG, Clark SA, Shankar S, Pan J, Clark LE, Yang P, Coscia A, McKay LGA, Varnum HH, Brusic V, Tolan NV, Zhou G, Desjardins M, Turbett SE, Kanjilal S, Sherman AC, Dighe A, LaRocque RC, Ryan ET, Tylek C, Cohen-Solal JF, Darcy AT, Tavella D, Clabbers A, Fan Y, Griffiths A, Correia IR, Seagal J, Baden LR, Charles RC, Abraham J. Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain. Science. 2022 Jan 21;375(6578):eabl6251. PMID:34855508 doi:10.1126/science.abl6251
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