Journal:Acta Cryst D:S2059798322007677
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| - | <StructureSection load='' size='450' side='right' scene=' | + | <StructureSection load='' size='450' side='right' scene='91/918482/Cv/1' caption=''> |
===Structural bases for the higher adherence to ACE2 conferred by the SARS-CoV-2 spike Q498Y substitution=== | ===Structural bases for the higher adherence to ACE2 conferred by the SARS-CoV-2 spike Q498Y substitution=== | ||
<big>Elena Erausquin, Fabian Glaser, Juan Fernández-Recio, Jacinto López-Sagaseta</big> <ref>doi: 10.1107/S2059798322007677</ref> | <big>Elena Erausquin, Fabian Glaser, Juan Fernández-Recio, Jacinto López-Sagaseta</big> <ref>doi: 10.1107/S2059798322007677</ref> | ||
<hr/> | <hr/> | ||
<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
| + | SARS-CoV-2 initiates infection of host cells by anchoring its viral envelope spike protein to the ACE2 receptor on the surface of human cells. Since its initial identification, a remarkable number of variants and other yet unmonitored lineages have been detected. Most of them harbor amino acid mutations in the spike protein with the potential to modulate the strength of the spike:ACE2 interaction. Further, some mutations can ultimately lead to immune evasion and reduction of the efficacy of existing vaccines. | ||
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| + | In this work, we study the molecular bases that underlie the enhanced adherence to ACE2 conferred by the mutation Q498Y, located in the SARS-CoV-2 spike receptor binding domain (RBD). This substitution has been found in SARS-CoV-2 human samples and others of unknown origin [GISAID DATABASE <ref>doi: 10.1038/s41467-022-28246-3</ref>]. | ||
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| + | <scene name='91/918482/Cv/2'>Composition of the asymmetric unit in the RBD Q498Y:ACE2 crystal</scene>. All RBD and ACE2 molecules are shown in individual colored cartoons. | ||
| + | *<scene name='91/918482/Cv/3'>Asymmetric unit copy 1</scene>. | ||
| + | *<scene name='91/918482/Cv/4'>Asymmetric unit copy 2</scene>. | ||
| + | *<scene name='91/918482/Cv/2'>Both copies of asymmetric unit</scene>. | ||
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| + | Our studies conclude that the increased affinity of the Q498Y RBD protein is due to a higher number and types of inter-molecular interactions provided by the RBD tyrosine 498 side chain, compared to those associated to glutamine 498 in the wild-type RBD. Comparison of the interatomic contacts between RBD and ACE2 in the wild type and Q498Y structures: | ||
| + | *<scene name='91/918482/Cv/10'>Interatomic polar interactions</scene> are shown as white dashed lines. The cut-off for Van der Waals and H-bonds are set to 4 Å and 3.4 Å, respectively. Interacting residues are depicted as sticks. | ||
| + | <jmol><jmolButton><script>frame 2 2 play; animation off; frame 2</script><text>only wild type structure</text></jmolButton><jmolButton><script>frame 1 1 play; animation off; frame 1</script><text>only Q498Y structure</text></jmolButton><jmolButton><script>animation off; frame all</script><text>both wild type and Q498Y</text></jmolButton></jmol> | ||
| + | *<scene name='91/918482/Cv1/2'>Interatomic non-polar interactions</scene> are indicated as dashed lines. | ||
| + | <jmol><jmolButton><script>frame 2 2 play; animation off; frame 2</script><text>only wild type structure</text></jmolButton><jmolButton><script>frame 1 1 play; animation off; frame 1</script><text>only Q498Y structure</text></jmolButton><jmolButton><script>animation off; frame all</script><text>both wild type and Q498Y</text></jmolButton></jmol> | ||
| + | *<scene name='91/918482/Cv1/3'>π-π stacking interaction established between the RBD Tyr498 and ACE2 Tyr41 aromatic rings</scene> | ||
| + | <jmol><jmolButton><script>frame 2 2 play; animation off; frame 2</script><text>only wild type structure</text></jmolButton><jmolButton><script>frame 1 1 play; animation off; frame 1</script><text>only Q498Y structure</text></jmolButton><jmolButton><script>animation off; frame all</script><text>both wild type and Q498Y</text></jmolButton></jmol> | ||
<b>References</b><br> | <b>References</b><br> | ||
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