Bajorath J, Aruffo A
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
J Biol Chem. 1994 Dec 23;269(51):32457-63.
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.
CD69被描述为一种T细胞活化抗原，但目前CD69的配体和生理功能尚不清楚。CD69细胞外结构域的序列与钙依赖性（C型）凝集素的序列有一些相似性。利用比较计算机建模和反向折叠计算，我们基于甘露糖结合蛋白的晶体结构生成并分析了CD69细胞外结构域的详细三维模型。CD69的序列似乎与C型凝集素折叠高度兼容，使用反向折叠计算对模型进行评估表明其总体正确性。与甘露糖结合蛋白和选择素相比，CD69在环区有明显缺失。此外，在C型凝集素家族中发现的形成保守钙结合位点的残基在CD69中并不保守。这表明CD69中存在一些结构特征，这些特征与在C型凝集素的两个晶体结构中看到的一些保守基序不同。CD69模型显示出由带电荷残基包围的腔状疏水区域。其中一个腔靠近一个潜在的低亲和力钙结合位点，可能与配体的特异性相互作用有关。
