Figure 4
From: Structural basis for the inhibition of HIV-1 Nef by a high-affinity binding single-domain antibody
Delineation of the sdAb19 surface binding epitope on Nef. (A) Display of amino acids on the surface of NefSF2 that interact with sdAb19. Polar residues E155, R188, K148, K192, H196, E201 and H203 surround hydrophobic residues V150, M198, L202, I137 as well as G134 and the central Y139 to constitute the binding epitope on Nef. (B) Surface display of the interacting residues in NefSF2. Basic residues are colored blue, acidic residue are colored red, and hydrophobic residues are colored yellow. The degree of sequence conservation for homologous residues in HIV-1 Nef alleles, subtype B, is shown in brackets. (C) Hydrophobic interactions are formed between M198 and L202 of Nef with L52 of sdAb19 in close proximity to the K148Nef–D60sdAb19 salt bridge. (D) Electrostatic surface display of the binding interface for sdAb19 in HIV-1 NefSF2. The electrostatic surface potential is colored from red (−4 kBT) to blue (+4 kBT). (E) Mutation K148E in Nef weakens the interaction by 44-fold compared to wild type SF2 Nef as determined by ITC.