OSCAR D1-D2 domain interface. (A) Comparison of D1-D2 interdomain angles among OSCAR, representative LRC receptors, and FcγRIII. D2 domains from OSCAR (magenta), p58-CL42 KIR (blue), GPVI (red), LILRB4 (gold), and FcγRIII (green) were superimposed to illustrate the relative positions of D1. For purposes of comparison, the degrees of rotation are defined such that at 0°, D1 would be doubled back and occupying the same position as D2 (see circle with arrows illustrating the clockwise rotation describing the relative positions of D1 domains). (B) Comparative views of the D1-D2 linker in FcαRI (top), GPVI (middle), and OSCAR (bottom). Conserved residues at the D1-D2 junction are shown as transparent spheres and color-coded according to their positions in the sequence alignment. Most LRC receptors have a Thr-Gly-Φ-Φ motif that creates a sharp bend in the D1-D2 linker sequence and packs the hydrophobic (Φ) residues after Gly against other hydrophobic residues in D2. In OSCAR, the mostly conserved Gly residue and the subsequent hydrophobic residue are replaced by 2 large, negatively charged Glu residues, sterically preventing formation of the sharp bend and hydrophobic cluster involving D2.