Fig. 3: SARS2-S D614G protein shows the prominent structural difference.

a, b Trimeric structure of the S proteins from SARS-CoV (a) and SARS-CoV-2 (b) that bind to the host receptor ACE2 (cyan). One protomer of the S protein is shown as a ribbon in navy (S1 subunit), orange (receptor-binding domain (RBD) in S1 subunit), and green (S2 subunit), while two other protomers are shown as gray transparent surfaces and ribbons. The structures are viewed from two different angles. c Comparison between wild-type (WT) and mutant S proteins from globally spread SARS-CoV-2 variants. (Inset) Enlargement of the region in which each amino acid is mutated, with comparison with the WT S protein. H49Y; as the histidine at position 49 is located distant from the RBD and putative cleavage sites, the effect of this mutation on S’s function is likely limited. V367F; the substitution from a valine to a phenylalanine at position 367 in the RBD introduces a larger side chain at a protomer–protomer interface, which might provide a more rigid RBD structure. G476S; the substitution at position 476 in the RBD results in a protruded surface, which appears to interfere with the ACE2–RBD interaction. V483A; both valine and alanine residues have short side chains, likely sharing similar phenotypes. D614G; details are depicted in Fig. 3d. Note that these structural bases are largely consistent with the results of cell entry activity shown in Fig. 2b. d Structural difference between WT and D614G SARS-CoV-2 S proteins. WT (left); an aspartic acid (D614) in the S1 subunit (navy) of a protomer binds to a threonine (T859) and/or a lysine (K854) in the S2 subunit (green) of the other protomer though electrostatic interaction between the pairs of these residues. D614G (right); the short nonpolar side chain of glycine (G614), which does not bind to T859 and K854, provides flexible space between the two protomers. The figures were drawn with PyMOL ver. 2.4 (https://pymol.org).