Fig. 2: Molecular switch of regulating the RBD orientation.

a,b, Structural basis of the interprotomer interaction networks around the clinical mutation sites for RBD-up (a) and RBD-down (b). The inset on the upper left corner of each panel illustrates the overall conformation of one protomer with the mutation site indicated by a box, which is expanded in the corresponding panel. The RBD-up and RBD-down protomers are colored in light blue (chain A) and pink (chain B), respectively. For RBD-down, the corresponding protomer, chain B, interacts with another RBD-down protomer, chain C, which is colored in light green. The positions of the salt bridges are highlighted in filled light blue circles. c, Comparison of the relative domain orientations of RBD-up and RBD-down in the context of the clinical mutations. The COMs of NTD (residues 1–288), RBD (residues 330–525), SD2 (residues 317–329 and 526–588) and SD1 (residues 290–316 and 589–695) are shown in spheres over the semitransparent cartoon representations of RBD-up (light blue) and RBD-down (pink). The two mutated residues, D614G and A570D, along with D571 on the same protomer, and K854 and K964 on the other protomer (indicated by an apostrophe), are shown in spheres. The α helix and the preceding loop in which K854’ and K964’ reside are shown in a cartoon representation and colored in green. d,e, Schematic representations of the domain motions of RBD-up (d) and RBD-down (e) modulated by the interprotomer salt bridges. A switch in salt bridge pairing between K964’ and D571/A570D is proposed to regulate the pedal-bin-like motions of RBD and domain D.