Fig. 2.

IGHV5-51 V2p mAbs define a binding class with a distinct mode of recognition. a Logogram of global V2 sequences in the HIV-1 LANL database, showing the relative amino acid frequencies (y-axis) at each position in V2 (x-axis, residues 165-182). Key hydrophobic amino acids bound by IGHV5-51 antibodies are highlighted in darker red, while other key contact residues are coloured black. b A cartoon representation of the three IGHV5-51 V2p Fab paratopes (coloured as in Fig. 1), with the central hydrophobic binding depression shown in surface view. Heavy and light chain residues that make up the hydrophobic binding area are indicated, and the side chains are shown for key buried V2 residues 172, 175 and 176. c The solvent accessible surfaces of the heavy and light chain variable domains from all three mAbs are shown and labelled. The light chains are coloured dark grey, while the heavy chains are coloured on a smoothed charge gradient with more electronegative regions in red, and more electropositive surfaces in blue. The heavy chain complementarity determining regions 1, 2 and 3 are encircled with green, yellow and pink dotted lines, respectively, and the CDR-H3 lengths and overall charges are indicated. V2 peptides are shown in stick and cartoon views. A single rotamer change to account for crystal packing is indicated by the asterisk. d Atomic level details of the interaction between all three IGHV5-51 mAb heavy chains and V2, with the CDRs coloured as in c. Hydrogen bonds are indicated with the dotted black lines, and key water molecules are shown with blue spheres. Alternative rotamer conformations for V1V2 residue D180 and CDR-H1 residue R28 (influenced by crystal packing in the CAP225 bound structure) are shown and labelled with asterisks