Fig. 4: Structural biology of H11-H4 bound to spike and RBD.

a, EM structure of spike (S1) trimer with each of three chains bound to one H11-H4 nanobody. The ‘up’ configured monomer is colored light pink, with the RBD highlighted in red. The other monomers are colored pale cyan and wheat throughout. Each spike monomer has bound one H11-H4 nanobody; the three H11-H4 nanobodies are colored yellow. b, Crystal structures of the H11-H4–RBD and H11-D4–RBD complexes were superimposed via the RBD (red), showing that both nanobodies recognize the same RBD epitope. H11-D4 is colored orange and H11-H4 yellow. c, The superimposed nanobodies in b show a 7° pivot between H11-H4 and H11-D4. d, Loops CDR1, CDR2 and CDR3 of H11-H4 control recognition and are highlighted in magenta. e, A 90° rotation of the structure shown in d, showing the residues in contact with RBD. H11-H4 residues are labeled in yellow, with carbon atoms colored yellow, nitrogen atoms blue and oxygen atoms red. RBD is shown as a white surface with contact points (<4.0 Å) highlighted in red. f, The same view as in c, showing the RBD residues in contact with H11-H4 (omitted). RBD residues are labeled in black, with carbons colored in gray and other atoms as in c. g, LigPlot⁴² of the interaction between H11-H4 (residues shown in gold, top) and RBD (residues shown in red, below). Hydrogen bonds are shown as black dashes and van der Waals interactions as light gray dashes. h, Arg52 of H11-H4 CDR2 stacks against the Phe490 of RBD and makes salt bridge contacts with Glu484. In addition, Arg52 makes hydrogen bonds with the main-chain Ser103 (side chain omitted) and Tyr109. H11-H4 residues are colored as in e. RBD residues are colored as in f.