title: Storage function of cartilage oligomeric matrix protein: the crystal structure of the coiled-coil domain in complex with vitamin D(3).
abstract: 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 A 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 approximately 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 beta-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.
authors.affiliation: Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Suat.Oezbek@unibas.ch
authors.forename: Suat
authors.initials: S
authors.lastname: Ozbek
authors.forename: Jürgen
authors.initials: J
authors.lastname: Engel
authors.forename: Jörg
authors.initials: J
authors.lastname: Stetefeld
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D018360:Crystallography, X-Ray; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D064235:Matrilin Proteins; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014801:Vitamin A / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000737:chemistry / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D008024:Ligands; D064235:Matrilin Proteins; D011993:Recombinant Fusion Proteins; D012177:Retinol-Binding Proteins; D014809:Vitamin D-Binding Protein; D014801:Vitamin A; D002117:Calcitriol