7yr2

From Proteopedia

SARS-CoV-2 BA.2.75 S Trimer in complex with ACE2(state1)

Structural highlights

7yr2 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:	Electron Microscopy, Resolution 3.3Å
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

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity for host receptor angiotensin-converting enzyme 2 (ACE2) than BA.5 and other variants. Structural analyses of BA.2.75 spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the "up" conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough-infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations.

Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75.,Cao Y, Song W, Wang L, Liu P, Yue C, Jian F, Yu Y, Yisimayi A, Wang P, Wang Y, Zhu Q, Deng J, Fu W, Yu L, Zhang N, Wang J, Xiao T, An R, Wang J, Liu L, Yang S, Niu X, Gu Q, Shao F, Hao X, Meng B, Gupta RK, Jin R, Wang Y, Xie XS, Wang X Cell Host Microbe. 2022 Nov 9;30(11):1527-1539.e5. doi: , 10.1016/j.chom.2022.09.018. Epub 2022 Oct 4. PMID:36270286^[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
↑ Cao Y, Song W, Wang L, Liu P, Yue C, Jian F, Yu Y, Yisimayi A, Wang P, Wang Y, Zhu Q, Deng J, Fu W, Yu L, Zhang N, Wang J, Xiao T, An R, Wang J, Liu L, Yang S, Niu X, Gu Q, Shao F, Hao X, Meng B, Gupta RK, Jin R, Wang Y, Xie XS, Wang X. Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75. Cell Host Microbe. 2022 Nov 9;30(11):1527-1539.e5. PMID:36270286 doi:10.1016/j.chom.2022.09.018