Fig. 1

MHCI gene family, and conservation of PDZ ligand motifs in MHCI cytoplasmic domains. a Greatly simplified schematic of the MHCI genomic region in humans (HLA, on chromosome 6, top) and mice (H2, on chromosome 17, bottom), showing the relative positions of the classical (black boxes) and non-classical (white boxes) MHCI genes or gene families. Multi-member gene clusters are indicated by breaks in the chromosome. Numerous genes and pseudogenes have been omitted for clarity, and distances are not to scale. Centromeric is to the left. Adapted from [62]. b Logo showing conservation of amino acids within closest-match homologues of the human classical MHCI HLA-A. The height of each letter corresponds to the extent of conservation across species. Color code: ST, orange; YFWCMVILA, green; DE, red; all others black. Below, individual source sequences. Putative PDZ ligand motifs are in red. Previously noted conserved serine and tyrosine residues that can be phosphorylated in some species (underlined in bold in b and c; see text) are embedded in PDZ ligand motifs in several MHCI proteins. Similar alignments have been performed previously (e.g., [15]). * = conserved; : = semi-conserved; . = similar. c Aligned amino acid sequences of the cytoplasmic domains of human MHCI proteins, with putative PDZ ligand motifs highlighted (class 1PDZ ligand, orange; class 2, blue; class 3, purple). Consensus motifs: class 1 PDZ, S/T-X-Y/F/W/C/M/V/I/L/A; class 2 PDZ, ΦXΦ (Y/F/W/C/M/V/I/L/A-X-Y/F/W/C/M/V/I/L/A); class 3 PDZ, D/E-X-Y/F/W/C/M/V/I/L/A [49]. Human reference sequences obtained from NCBI, alignments performed using T-Coffee [34]. d Conservation of PDZ ligands across human HLA genes from c, despite non-conservative substitutions. In two cases, a class 1 ligand motif is converted to class 2 by the substitution (2), but remains a putative PDZ ligand. Color code as in (b)