Covariance of Charged Amino Acids at Positions 322 and 440 of HIV-1 Env Contributes to Coreceptor Specificity of Subtype B Viruses, and Can Be Used to Improve the Performance of V3 Sequence-Based Coreceptor Usage Prediction Algorithms
Figure 3
Three-dimensional model of the CD4-bound gp120 containing V3 and C4 docked to a CCR5 N-terminus peptide.
(A) The gp120 molecule is shown in ribbon representation, the V3 is shown in grey and the C4 region is shown in blue. The CCR5 N-terminus peptide is shown in ribbon representation (red) with wire mesh van der Waals surface representation, and the amino acids are shown in stick representation. Asp11 in the CCR5 N-terminus and Glu322 and Arg440 in gp120 are shown in stick representation and colored according to charge; positively charged residues are colored blue and negatively charged residues colored red. (B, C) Close up of gp120 and the CCR5 N-terminus peptide interface is represented as described above. Notably, CCR5 N-terminus mesh surface representation and amino acid stick representation was removed, and mesh surface van der Waals surface representation was added to Asp11 in the CCR5 N-terminus, Arg440 (B) and Lys 440 (C). (D) Three-dimensional model of CD4-bound gp120 containing V3 and C4 docked to the CCR5 N-terminus (to aid visual distinction between gp120 and the CCR5 N-terminus peptide) with (E) original Glu322/Arg440 genotype or (F) mutated Arg322/Glu440 genotype, shown in surface charge representation colored according to charge. The number of hydrogen bonds (NHB) and salt bridges (NSB) predicted to form at the interface between gp120 and the CCR5 N-terminus was calculated using PISA software.