FIGURE 4.

Amino acid alignment of DOα common alleles and variants analyzed.

(A) Alignment of the four common DOα alleles to DOA*0101. Dashes indicate similarity and the dots indicate a truncated protein (for DOA*0104). Missense and the stop mutation for the 21 DOA variants selected for the screen are indicated below the amino acid sequences for the common variants. DOα alleles that form DO proteins with decreased function relative to DOA*0101/DOB*0101 are colored red, those with increased function in blue and those in black have normal function (see Fig. 5). DOA protein domains are marked by colored frames as indicated.

(B) The structure of the DM-DO complex (2) with the side-chains of amino acids mutated in the DOA variants investigated in this study shown as spheres. The backbone cartoon of DMA is shown in light green and of DMB in dark green. DOA, carrying the mutated residues, is depicted in dark orange and DOB in light orange. As in (A), residues with enhanced function are colored blue, those leading to reduced function in red and mutations without an effect on functionality are shown in grey. Mutations occurring in the transmembrane region are show as the crystal structure did not contain this domain. The Figure was created by PyMol (56) utilizing the PDB file 4I0P.