Figure 3
From: HIV-1 Nef interaction influences the ATP-binding site of the Src-family kinase, Hck
Molecular models of HIV-1 Nef in complex with wild-type and high-affinity RT loop SH3 domains (SH3-HART). A) Molecular model of HIV-1 Nef (cyan) in complex with the SH3 domain of Fyn (red) in which RT loop Arg96 was replaced with isoleucine (I96) to resemble the Hck SH3 domain (PDB: 1EFN[22, 49]). B) Close-up view of the wild-type interaction interface. SH3 domain RT loop Ile96 (red spheres) interacts with conserved hydrophobic residues of Nef that form a hydrophobic pocket (F90, W113, Y120). The interaction is stabilized by ion pairing of SH3 Asp100 (D100) and Nef Arg77 (R77) in the conserved PxxPxR motif (dotted lines). C) To enhance Nef interaction with SH3, the wild-type RT loop sequence E94AIHRE was replaced with the sequence T94SPFPW, which was previously reported to result in high affinity Nef-SH3 interaction [30]. The side chains of the six modified residues are modeled in green. Note that SH3-HART Phe97 (F97; green spheres) occupies the position of I96 in the wild-type crystal structure. Recent crystallographic analysis of a related high affinity Nef-SH3 interface supports this model [29].