A structural basis for the unique binding features of the human vitamin D-binding protein

The human serum vitamin D-binding protein (DBP) has many physiologically important functions, ranging from transporting vitamin D-3 metabolites, binding and sequestering globular actin and binding fatty acids to functioning in the immune system. Here we report the 2.3 Angstrom crystal structure of DBP in complex with 25-hydroxyvitamin D-3, a vitamin D3 metabolite, which reveals the vitamin D-binding site in the N-terminal part of domain I. To more explicitly explore this, we also studied the structure of DBP in complex with a vitamin D3 analog. Comparisons with the structure of human serum albumin, another family member, reveal a similar topology but also significant differences in overall, as well as local, folding. These observed structural differences explain the unique vitamin D-3-binding property of DBP.