Nef Alleles from All Major HIV-1 Clades Activate Src-Family Kinases and Enhance HIV-1 Replication in an Inhibitor-Sensitive Manner
Figure 2
Structural features of the Nef:SH3 and Nef dimerization interfaces.
A) Overview of the Nef:SH3 dimer X-ray crystal structure, based on the crystal coordinates of Lee, et al. (PDB: 1EFN) [48]. The monomeric Nef core subunits are modeled in blue and green respectively; the SH3 domains are shown in red. B) Close-up view of the Nef:SH3 interface. Nef residues P72 and P75 define a polyproline type II helix that meshes with the hydrophobic grooves of the SH3 surface, and is oriented and stabilized by an ionic interaction between Nef R77 and SH3 D100. High affinity interaction also requires a hydrophobic pocket formed in part by Nef residues F90, W113, and Y120. This pocket engages SH3 domain RT loop I96 (Van der Waals surface shown as dots). Mutagenesis of either Nef Y120 or SH3 I96 is sufficient to disrupt Nef:SH3 interaction [50], [66]. C) Close-up view of the Nef dimerization interface. Dimer packing involves hydrophobic interactions of side chains of the αB helices (L112, Y115, F121) which are orthogonally opposed. This hydrophobic core is capped on both ends by ionic interactions involving D123 and R105.