Molecular model of the extracellular lectin-like domain in CD69

CD69 is described as a T cell activation antigen, but the ligand and physiological function of CD69 are currently unknown. The sequence of the extracellular domain of CD69 shows some similarity with that of calcium-dependent (C-type) lectins. Using comparative computer modeling and inverse folding calculations, we have generated and analyzed a detailed three-dimensional model of the extracellular domain of CD69 based on the crystal structure of the mannose binding protein. The sequence of CD69 appears to be highly compatible with the C-type lectin fold, and assessment of the model using inverse folding calculations suggests its overall correctness. Compared with mannose binding protein and the selectins, CD69 displays significant deletions in loop regions. In addition, residues that form conserved calcium binding sites found in the C-type lectin family are not conserved in CD69. This suggests the presence of structural features in CD69 that depart from some of the conserved motifs seen in two crystal structures of C-type lectins. The CD69 model shows cavity-shaped hydrophobic regions surrounded by charged residues. One of these cavities is proximal to a potential low affinity calcium binding site and may be implicated in specific interactions with ligands.