Fig. 5. Partially folded intermediate state of the spike protein.

(A) Schematic derived from a CG-MM simulation guided by the tomographic densities of partially folded intermediate states of S2 spanning the viral and host membranes. (B, E, H, L, and N) Contrast-inverted slices from tomograms of VLPs bearing S and tEVs bearing hACE2, showing densities attributable to the partially folded intermediate state of S. (C, F, I to K, M, and O) Enlarged regions from tomogram slices showing densities attributable to S partially folded intermediates (purple arrowheads) linking VLP and tEV membranes. (D and G) Isosurface representations of (C) and (F) with the postfusion S (PDB ID: 6M3W) fitted into the map density. Movie from z slices of tomogram displayed in (K) and (M) is shown as movies S2 and S3, respectively. Scale bars, (B, E, H, L, and N) 50 nm and (C, D, F, G, I to K, M, and O) 10 nm.