8asy

SARS-CoV-2 Omicron BA.2.75 RBD in complex with ACE2SARS-CoV-2 Omicron BA.2.75 RBD in complex with ACE2

Structural highlights

8asy is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.85Å
Ligands:	, , ,
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

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused successive global waves of infection. These variants, with multiple mutations in the spike protein, are thought to facilitate escape from natural and vaccine-induced immunity and often increase in affinity for ACE2. The latest variant to cause concern is BA.2.75, identified in India where it is now the dominant strain, with evidence of wider dissemination. BA.2.75 is derived from BA.2 and contains four additional mutations in the receptor-binding domain (RBD). Here, we perform an antigenic and biophysical characterization of BA.2.75, revealing an interesting balance between humoral evasion and ACE2 receptor affinity. ACE2 affinity for BA.2.75 is increased 9-fold compared with BA.2; there is also evidence of escape of BA.2.75 from immune serum, particularly that induced by Delta infection, which may explain the rapid spread in India, where where there is a high background of Delta infection. ACE2 affinity appears to be prioritized over greater escape.

A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75.,Huo J, Dijokaite-Guraliuc A, Liu C, Zhou D, Ginn HM, Das R, Supasa P, Selvaraj M, Nutalai R, Tuekprakhon A, Duyvesteyn HME, Mentzer AJ, Skelly D, Ritter TG, Amini A, Bibi S, Adele S, Johnson SA, Paterson NG, Williams MA, Hall DR, Plowright M, Newman TAH, Hornsby H, de Silva TI, Temperton N, Klenerman P, Barnes E, Dunachie SJ, Pollard AJ, Lambe T, Goulder P, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR Cell Rep. 2023 Jan 31;42(1):111903. doi: 10.1016/j.celrep.2022.111903. Epub 2022 , Dec 14. PMID:36586406^[4]

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

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:http://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:http://dx.doi.org/10.1038/nature02145
↑ Huo J, Dijokaite-Guraliuc A, Liu C, Zhou D, Ginn HM, Das R, Supasa P, Selvaraj M, Nutalai R, Tuekprakhon A, Duyvesteyn HME, Mentzer AJ, Skelly D, Ritter TG, Amini A, Bibi S, Adele S, Johnson SA, Paterson NG, Williams MA, Hall DR, Plowright M, Newman TAH, Hornsby H, de Silva TI, Temperton N, Klenerman P, Barnes E, Dunachie SJ, Pollard AJ, Lambe T, Goulder P, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR. A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75. Cell Rep. 2022 Dec 14:111903. doi: 10.1016/j.celrep.2022.111903. PMID:36586406 doi:http://dx.doi.org/10.1016/j.celrep.2022.111903

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OCA

[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] Huo J, Dijokaite-Guraliuc A, Liu C, Zhou D, Ginn HM, Das R, Supasa P, Selvaraj M, Nutalai R, Tuekprakhon A, Duyvesteyn HME, Mentzer AJ, Skelly D, Ritter TG, Amini A, Bibi S, Adele S, Johnson SA, Paterson NG, Williams MA, Hall DR, Plowright M, Newman TAH, Hornsby H, de Silva TI, Temperton N, Klenerman P, Barnes E, Dunachie SJ, Pollard AJ, Lambe T, Goulder P, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR. A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75. Cell Rep. 2022 Dec 14:111903. doi: 10.1016/j.celrep.2022.111903. PMID:36586406 doi:http://dx.doi.org/10.1016/j.celrep.2022.111903

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