An Evolutionary Analysis of Antigen Processing and Presentation across Different Timescales Reveals Pervasive Selection
Figure 3
Analysis of positively selected sites.
In all panels aminoacid numbering refers to the human protein. (A) Left: ribbon diagram of the extracellular domain of human CD1D bound to α-galactosylceramide (orange). Positively selected sites are shown in red, the α1/α2 and α3 domains are depicted in dark and light grey, respectively. Yellow residues form the contact interface with the TcR. Right: alignment of the transmembrane and cytoplasmic domains of CD1D for a few representative mammals; positively selected sites are in red and the YxxZ sequence is marked (blue line); the green asterisk denotes a site positively selected in the human lineage. (B) Surface structure of the protease domain of human CTSG; sites that define substrate binding pockets or form the catalytic triad are shown in yellow; positively selected sites are in red (whole phylogeny) and green (simians). The violet residue confers to CTSG the ability to cleave Shigella virulence factors if mutated. 126R is not visible as it is located on the back surface. (C) Left: ribbon diagram of the human CD207 CRD. Color codes are as follows: yellow, sites directly involved in sugar binding; green, positively selected site at the sugar binding interface; brown, sites involved in trimer formation; orange, nonsynonymous SNPs; magenta, positively selected site that is polymorphic in humans; black, missense SNP at the sugar binding interface; blue, a human mutation responsible for Birbeck granule deficiency. Right: alignment of a portion of the CRD for a few representative mammals; color codes are as in the left panel. (D) Positively selected sites for CYBB are shown relative to the membrane topology (left); sites subject to diversifying selection are in red, mutations responsible for CGD or MSMD are in blue (note that mutations are shown only if falling in the region where positively selected sites are located); glycosylation sites are represented in green; the magenta arrows denote the region which is represented in the multiple species alignment (right, color codes as in the membrane topology diagram). (E) Membrane topology arrangement and positively selected sites for TAP1; TAP2 (green profiled) is shown although no positively selected sites were identified. The TAP1 unique N-terminal domain is shown as grey cylinders, the ABC transporter domain is in blue; the nucleotide binding domain is in orange and the protein portions that bind peptides are profiled in red. Sites subject to diversifying selection are in red, human missense polymorphisms in black, positively selected sites in the human lineage are in green. (F) Ribbon diagram of human tapasin; positively selected sites are shown in red; the 87 N-terminal aminoacids that facilitate the folding of MHC I-peptide complexes are in light blue. (G) Left: ribbon diagram of human BLMH (one subunit of the hexameric complex is shown); positively selected sites are in red, the acetylated/ubiquitinated lysine (391K) is in violet, the catalytic triad in yellow. Right: alignment of the region surrounding 391K and two positively selected sites for a few representative mammals; color codes as in the left panel.