Storage function of cartilage oligomeric matrix protein: the crystal structure of the coiled‐coil domain in complex with vitamin D3

The five‐stranded coiled‐coil domain of cartilage oligomeric matrix protein (COMPcc) forms a continuous axial pore with binding capacities for hydrophobic compounds, including prominent cell signalling molecules. Here, we report the X‐ray structure of the COMPcc domain in complex with vitamin D3 at 1.7 Å resolution. The COMPcc pentamer harbours two molecules of the steroid hormone precursor in a planar s‐trans conformation of the conjugated triene, with the aliphatic tails lying along the molecule axis. A hydrophilic ring of five Gln54 side chains divides the channel into two hydrophobic compartments in which the bound vitamin D3 pair is fixed in a head‐to‐head orientation. Vitamin D3 binding induces a volumetric increase of the cavities of ∼30% while the main chain distances of the pentamer are retained. This adaptation to the bulky ring systems of the ligands is accomplished by a rotamer re‐orientation of β‐branched side chains that form the knobs into holes of the coiled‐coil structure. Compared with binding of vitamin D and retinoic acid by their classical receptors, COMP exerts a distinct mechanism of interaction mainly defined by the pattern of hydrophobic core residues.