(a) Domain structure of the S-protein. UH, upstream helix; HR1, heptad repeat 1; CH, central helix; CD, connector domain; HR2, heptad repeat 2. TM, transmembrane segment. Segments colored in white are not part of the expressed ectodomain construct. (b) Three views of the unsharpened cryo-EM map contoured at 6.0 RMS. The S1 and S2 regions are colored cyan and magenta, respectively. (c) The portion of the cryo-EM map corresponding to the S1 region contoured at 5.0 RMS. Each subunit is colored differently. (d) Domain structure of an S1 subunit shown within a transparent rendering of the cryo-EM map. The highly ordered N-glycan (Asn 62) found in the center of the S1 subunit is shown in stick representation. The three receptor binding loops of the RBD (domain B) are labeled. (e) A portion of the cryo-EM map showing the S1 region viewed from the top. The three RBDs are shown as ribbons. (f) The portion of the cryo-EM map corresponding to the S2 region contoured at 3.0 RMS. Each subunit is colored differently. (g) Ribbon representation of the S2 subunit. (h) In the down conformation, the RBD (domain B, orange) makes polar interactions (cyan sidechains) with the CH-HR1 junction and hydrophobic interactions (magenta sidechains) in the elbow between domain B and domain C. The dotted arrow shows the direction that the RBD will take on conversion to the up conformation.