N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2

SARS-CoV-2 is spreading around the world for the past year. Recently, several variants such as B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma), sharing a key mutation N501Y on the RBD, appear to be more infectious to humans. To understand the underlying mechanism, we performed cell surface binding assay, kinetics study, single-molecule technique, and computational method to investigate the interaction between these RBD (mutations) and ACE2. Remarkably, RBD with the N501Y mutation exhibited a considerably stronger interaction, with a faster association rate and slower dissociation rate. Consistently, atomic force microscopy-based single-molecule force microscopy quantifies their strength showing a higher binding probability and unbinding force for the mutation. Molecular dynamics simulations of RBD-ACE2 complexes indicated that the N501Y introduced additional π-π and π-cation interaction for the higher force/interaction. Taken together, we suggested that the reinforced interaction from N501Y mutation in RBD should play an essential role in the higher transmission of SARS-CoV-2 variants and future mutations in the RBD of the virus should be under surve illance.
Source: eLife - Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research