7pki

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Crystal structure of human ACE2 bound to the spike receptor-binding domain from a cave bat sarbecovirus closely related to SARS-CoV-2.

Structural highlights

7pki is a 2 chain structure with sequence from Homo sapiens and Sarbecovirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.9423413Å
Ligands:CL, GOL, NAG, PEG, SO4, TRS, 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

The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats(1-4), including the closest virus from R. affinis, RaTG13 (refs. (5,6)), and pangolins(7-9). SARS-CoV-2 has a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range(10-12). SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 (hACE2) pathway have not yet been identified, although they would be key in understanding the origin of the epidemic. Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula. We found that the receptor-binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than that of the SARS-CoV-2 strain isolated in Wuhan from early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies that neutralize SARS-CoV-2. None of these bat viruses contains a furin cleavage site in the spike protein. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses that are potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.

Bat coronaviruses related to SARS-CoV-2 and infectious for human cells.,Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, Regnault B, Douangboubpha B, Karami Y, Chretien D, Sanamxay D, Xayaphet V, Paphaphanh P, Lacoste V, Somlor S, Lakeomany K, Phommavanh N, Perot P, Dehan O, Amara F, Donati F, Bigot T, Nilges M, Rey FA, van der Werf S, Brey PT, Eloit M Nature. 2022 Apr;604(7905):330-336. doi: 10.1038/s41586-022-04532-4. Epub 2022 , Feb 16. PMID:35172323[4]

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

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Citations
48 reviews cite this structure
The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines.
McLean et al. (2022)
47 more
143 other articles
No citations found

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. ↑ Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, Regnault B, Douangboubpha B, Karami Y, Chretien D, Sanamxay D, Xayaphet V, Paphaphanh P, Lacoste V, Somlor S, Lakeomany K, Phommavanh N, Perot P, Dehan O, Amara F, Donati F, Bigot T, Nilges M, Rey FA, van der Werf S, Brey PT, Eloit M. Bat coronaviruses related to SARS-CoV-2 and infectious for human cells. Nature. 2022 Apr;604(7905):330-336. doi: 10.1038/s41586-022-04532-4. Epub 2022 , Feb 16. PMID:35172323 doi:http://dx.doi.org/10.1038/s41586-022-04532-4

Contents


PDB ID 7pki

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