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Storage function of cartilage oligomeric matrix protein: the crystal structure of the coiled‐coil domain in complex with vitamin D 3
Author(s) -
Özbek Suat,
Engel Jürgen,
Stetefeld Jörg
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf628
Subject(s) - basel i , cartilage oligomeric matrix protein , basel ii , medicine , economics , osteoarthritis , alternative medicine , pathology , microeconomics , capital requirement , incentive
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 D 3 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 D 3 pair is fixed in a head‐to‐head orientation. Vitamin D 3 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.