Fig. 1: Cryo-EM structure of the C144–S complex illustrates a distinct VH3-53 NAb binding mode.
From: SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies
a, 3.2 Å cryo-EM density for the C144–S trimer complex revealing C144 binding to a closed (three down RBDs) spike conformation. LC, light chain; HC, heavy chain. b, Overlay of C102 Fab (from C102–RBD crystal structure) (Extended Data Fig. 1) and C144 Fab (from C144–S structure) aligned on a RBD monomer. RBD residues corresponding to the ACE2 epitope (orange-red cartoon) are shown on the same RBD for reference. C144 adopts a distinct conformation relative to the C102-like VH3-53-encoded short CDRH3 NAb class, allowing binding to the down RBD conformation on trimeric spike, whereas C102-like NAbs can only bind to up RBDs. c, Quaternary epitope of C144 involving bridging between adjacent RBDs via the CDRH3 loop (illustrated as thicker ribbon). d, e, Close-up view of CDRH3-mediated contacts on adjacent protomer RBD (dark grey). C144 CDRH3 residues F100D and W100E are buried in a hydrophobic pocket comprising the RBD α1 helix, residue F374RBD and the N343RBD glycan. f, Surface representation of C144 epitope (light blue) across two adjacent RBDs. RBD epitope residues (defined as residues containing atom(s) within 4 Å of a Fab atom) are labelled in black.
