Storage function of cartilage oligomeric matrix protein: the crystal structure of the coiled-coil domain in complex with vitamin D3
AUTOR(ES)
Özbek, Suat
FONTE
Oxford University Press
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=137217Documentos Relacionados
- Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface.
- Presence of two distinct regions in the coiled-coil structure of the streptococcal Pep M5 protein: relationship to mammalian coiled-coil proteins and implications to its biological properties.
- NuMA/centrophilin: sequence analysis of the coiled-coil rod domain.
- The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding
- Predicting specificity in bZIP coiled-coil protein interactions