7fc3
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7fc3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Equus_caballus Equus caballus] and [https://en.wikipedia.org/wiki/Human_coronavirus_NL63 Human coronavirus NL63]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FC3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7fc3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Equus_caballus Equus caballus] and [https://en.wikipedia.org/wiki/Human_coronavirus_NL63 Human coronavirus NL63]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FC3 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.19Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7fc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fc3 OCA], [https://pdbe.org/7fc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fc3 RCSB], [https://www.ebi.ac.uk/pdbsum/7fc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fc3 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7fc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fc3 OCA], [https://pdbe.org/7fc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fc3 RCSB], [https://www.ebi.ac.uk/pdbsum/7fc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fc3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and human coronavirus (hCoV)-NL63 utilize ACE2 as the functional receptor for cell entry, which leads to zoonotic infection. Horses (Equus caballus) attracted our attention because the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 and SARS-CoV-2-related coronaviruses bind equine ACE2 (eACE2) with high affinity. Here we show that eACE2 binds the RBDs of these three coronaviruses and also SARS-CoV-2 variants but with lower affinities compared with human ACE2 (hACE2). Structural analysis and mutation assays indicated that eACE2-H41 accounts for the lower binding affinity of eACE2 to the RBDs of SARS-CoV-2 variants (Alpha, Beta, and Gamma), SARS-CoV, and hCoV-NL63. Pseudovirus infection assays showed that the SARS-CoV-2 Delta strain (B.1.617.2) displayed a significantly increased infection efficiency in eACE2-expressing HeLa cells. Our results reveal the molecular basis of eACE2 binding to the RBDs of SARS-CoV, SARS-CoV-2, and hCoV-NL63, which provides insights into the potential animal transmission of these ACE2-dependent coronaviruses. | Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and human coronavirus (hCoV)-NL63 utilize ACE2 as the functional receptor for cell entry, which leads to zoonotic infection. Horses (Equus caballus) attracted our attention because the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 and SARS-CoV-2-related coronaviruses bind equine ACE2 (eACE2) with high affinity. Here we show that eACE2 binds the RBDs of these three coronaviruses and also SARS-CoV-2 variants but with lower affinities compared with human ACE2 (hACE2). Structural analysis and mutation assays indicated that eACE2-H41 accounts for the lower binding affinity of eACE2 to the RBDs of SARS-CoV-2 variants (Alpha, Beta, and Gamma), SARS-CoV, and hCoV-NL63. Pseudovirus infection assays showed that the SARS-CoV-2 Delta strain (B.1.617.2) displayed a significantly increased infection efficiency in eACE2-expressing HeLa cells. Our results reveal the molecular basis of eACE2 binding to the RBDs of SARS-CoV, SARS-CoV-2, and hCoV-NL63, which provides insights into the potential animal transmission of these ACE2-dependent coronaviruses. | ||
| - | Structural insights into the binding of SARS-CoV-2, SARS-CoV, and hCoV-NL63 spike receptor-binding domain to horse ACE2.,Lan J, Chen P, Liu W, Ren W, Zhang L, Ding Q, Zhang Q, Wang X, Ge J Structure. 2022 | + | Structural insights into the binding of SARS-CoV-2, SARS-CoV, and hCoV-NL63 spike receptor-binding domain to horse ACE2.,Lan J, Chen P, Liu W, Ren W, Zhang L, Ding Q, Zhang Q, Wang X, Ge J Structure. 2022 Oct 6;30(10):1432-1442.e4. doi: 10.1016/j.str.2022.07.005. Epub , 2022 Aug 1. PMID:35917815<ref>PMID:35917815</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7fc3" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7fc3" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Spike protein 3D structures|Spike protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
structure of NL63 receptor-binding domain complexed with horse ACE2
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