Fig. 4: Effect of dimerization on CCR5 and CXCR4 functional mechanism.

Estimates of the volume of the ligand binding site for each dimeric structure. A CCR5 homodimer. B CXCR4 homodimer. C CCR5–CXCR4 heterodimer. The volume calculation was performed on the structures obtained from the atomistic MD simulations, using 500 frames for each system. The boxplots illustrate the distribution of data, with the central box representing the interquartile range (IQR) bounded by the first and the third quartile. The line inside the box denotes the median, while the whiskers extend to the minimum and maximum values within 1.5 times the IQR. Data points beyond the whiskers are considered outliers and represented as dots. Values of the distance between TM3 and TM6 for each dimeric structure. D CCR5 homodimer. E CXCR4 homodimer. F CCR5–CXCR4 heterodimer. The values were obtained from the atomistic MD simulations (4500 frames per system). The same distances are calculated in the experimental structures (11 structures for CCR5, 6 for CXCR4) and reported as kernel density estimation (dashed lines). G Atomistic structure of CCR5 with reduced access to ligand binding site. H Detail of CCR5 with TM5-TM6 in open conformation. I Close-up of CXCR4 with TM5-TM6 in the closed conformation. Here, the reference monomeric structures for CCR5 and CXCR4 are reported as gray cartoons, while displacements are highlighted with red arrows.