Fig. 4: Cryo-EM structures of the SARS-CoV-2 S trimer in complex with 2H2 Fab.

a, b Side and top views of the S-2H2-F3a cryo-EM map (a) and pseudo atomic model (b). RBD-1 and RBD-2 are in up configuration, while RBD-3 is down, with each of the RBDs bound with a 2H2 Fab. Protomer 1, 2, and 3 are shown in light green, powder blue, and gold, respectively. This color scheme is followed throughout. Heavy chain and light chain of 2H2 Fab in royal blue and violet red, respectively. c, d Side and top views of the S-2H2-F2 cryo-EM map (c) and pseudo atomic model (d), with two up RBDs (RBD-1 and RBD-2) each bound with a 2H2 Fab. e, f 2H2 Fab-induced conformational changes of the S trimer. Shown is the structural comparation of RBDs between S-2H2-F1 (in color) and S-open (dim gray) (e), and between S-2H2-F3a (in color) and S-2H2-F2 (dim gray) (f). g 2H2 Fab mainly binds to the RBM (light sea green surface) of RBD, with major involved structural elements labeled. RBD core is rendered as light green surface. h 2H2 Fab (left) and ACE2 (right, gold, PDB: 6M0J) share overlapping epitopes on RBM (second row) and would clash upon binding to the S trimer. i, j The involved regions/residues forming potential contacts between the light chain (in violent red, i) or heavy chain (in royal blue, j) of 2H2 and the RBD-1 of S-2H2-F3a. Asterisks highlight residues also involved in the interactions with ACE2. Note that considering the local resolution limitation in the RBD-2H2 portion of the map due to intrinsic dynamic nature in these regions, we analyzed the potential interactions that fulfill criteria of both < 4 Å side chain distance cutoff and <8 Å main chain distance cutoff, which criteria were followed throughout.