Journal:Acta Cryst D:S2059798322007677

Structural bases for the higher adherence to ACE2 conferred by the SARS-CoV-2 spike Q498Y substitution

Elena Erausquin, Fabian Glaser, Juan Fernández-Recio, Jacinto López-Sagaseta ^[1]

Molecular Tour
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.

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; doi: 10.1038/s41467-022-28246-3].

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.

References

1. ↑ Erausquin E, Glaser F, Fernandez-Recio J, Lopez-Sagaseta J. Structural bases for the higher adherence to ACE2 conferred by the SARS-CoV-2 spike Q498Y substitution. Acta Crystallogr D Struct Biol. 2022 Sep 1;78(Pt 9):1156-1170. doi:, 10.1107/S2059798322007677. Epub 2022 Aug 25. PMID:36048155 doi:http://dx.doi.org/10.1107/S2059798322007677