8xln

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Structure of the SARS-CoV-2 EG.5.1 spike RBD in complex with ACE2Structure of the SARS-CoV-2 EG.5.1 spike RBD in complex with ACE2

Structural highlights

8xln 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 3.78Å
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

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.

Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant.,Tsujino S, Deguchi S, Nomai T, Padilla-Blanco M, Plianchaisuk A, Wang L, Begum MM, Uriu K, Mizuma K, Nao N, Kojima I, Tsubo T, Li J, Matsumura Y, Nagao M, Oda Y, Tsuda M, Anraku Y, Kita S, Yajima H, Sasaki-Tabata K, Guo Z, Hinay AA Jr, Yoshimatsu K, Yamamoto Y, Nagamoto T, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Nasser H, Jonathan M, Putri O, Kim Y, Chen L, Suzuki R, Tamura T, Maenaka K, Irie T, Matsuno K, Tanaka S, Ito J, Ikeda T, Takayama K, Zahradnik J, Hashiguchi T, Fukuhara T, Sato K Microbiol Immunol. 2024 Jul 4. doi: 10.1111/1348-0421.13165. PMID:38961765[4]

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

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. Tsujino S, Deguchi S, Nomai T, Padilla-Blanco M, Plianchaisuk A, Wang L, Begum MM, Uriu K, Mizuma K, Nao N, Kojima I, Tsubo T, Li J, Matsumura Y, Nagao M, Oda Y, Tsuda M, Anraku Y, Kita S, Yajima H, Sasaki-Tabata K, Guo Z, Hinay AA Jr, Yoshimatsu K, Yamamoto Y, Nagamoto T, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Nasser H, Jonathan M, Putri O, Kim Y, Chen L, Suzuki R, Tamura T, Maenaka K, Irie T, Matsuno K, Tanaka S, Ito J, Ikeda T, Takayama K, Zahradnik J, Hashiguchi T, Fukuhara T, Sato K. Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant. Microbiol Immunol. 2024 Jul 4. PMID:38961765 doi:10.1111/1348-0421.13165

8xln, resolution 3.78Å

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OCA