7wgc

From Proteopedia

Neutral Omicron Spike Trimer in complex with ACE2.

Structural highlights

7wgc is a 2 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 3.6Å
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

The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the spike (S) from Omicron reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of the viral fusion step. Alterations in local conformation, charge, and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Structure of the Omicron S bound with human ACE2, together with the analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members, as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies, sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron.,Cui Z, Liu P, Wang N, Wang L, Fan K, Zhu Q, Wang K, Chen R, Feng R, Jia Z, Yang M, Xu G, Zhu B, Fu W, Chu T, Feng L, Wang Y, Pei X, Yang P, Xie XS, Cao L, Cao Y, Wang X Cell. 2022 Mar 3;185(5):860-871.e13. doi: 10.1016/j.cell.2022.01.019. Epub 2022 , Jan 25. PMID:35120603^[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
↑ Cui Z, Liu P, Wang N, Wang L, Fan K, Zhu Q, Wang K, Chen R, Feng R, Jia Z, Yang M, Xu G, Zhu B, Fu W, Chu T, Feng L, Wang Y, Pei X, Yang P, Xie XS, Cao L, Cao Y, Wang X. Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron. Cell. 2022 Mar 3;185(5):860-871.e13. doi: 10.1016/j.cell.2022.01.019. Epub 2022, Jan 25. PMID:35120603 doi:http://dx.doi.org/10.1016/j.cell.2022.01.019