8df5

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SARS-CoV-2 Beta RBD in complex with human ACE2 and S304 Fab and S309 Fab

Structural highlights

8df5 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.
Method:X-ray diffraction, Resolution 2.7Å
Ligands:CL, EDO, 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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites-a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single-amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn(501)-->Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change-for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.

Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution.,Starr TN, Greaney AJ, Hannon WW, Loes AN, Hauser K, Dillen JR, Ferri E, Farrell AG, Dadonaite B, McCallum M, Matreyek KA, Corti D, Veesler D, Snell G, Bloom JD Science. 2022 Jul 22;377(6604):420-424. doi: 10.1126/science.abo7896. Epub 2022 , Jun 28. PMID:35762884[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ 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
  2. ↑ 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:http://dx.doi.org/10.1074/jbc.M002615200
  3. ↑ 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:http://dx.doi.org/10.1038/nature02145
  4. ↑ Starr TN, Greaney AJ, Hannon WW, Loes AN, Hauser K, Dillen JR, Ferri E, Farrell AG, Dadonaite B, McCallum M, Matreyek KA, Corti D, Veesler D, Snell G, Bloom JD. Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution. Science. 2022 Jul 22;377(6604):420-424. doi: 10.1126/science.abo7896. Epub 2022, Jun 28. PMID:35762884 doi:http://dx.doi.org/10.1126/science.abo7896

Contents


PDB ID 8df5

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OCA

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