Insight into Schmid Metaphyseal Chondrodysplasia from the Crystal Structure of the Collagen X NC1 Domain Trimer

• Published in: Structure (London) 2002-02, Vol.10 (2), p.165-173
• Main Authors: Bogin, Oren, Kvansakul, Marc, Rom, Eran, Singer, Josef, Yayon, Avner, Hohenester, Erhard
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Animals; Binding Sites; C1q-like domain; Calcium - metabolism; calcium binding; Collagen Type X - chemistry; Collagen Type X - genetics; collagen X; Crystallography, X-Ray; detergent binding; Exostoses, Multiple Hereditary - genetics; Exostoses, Multiple Hereditary - metabolism; genetic disorder; Humans; Models, Molecular; Molecular Sequence Data; Mutation, Missense; NC1 domain; Protein Binding; Protein Structure, Quaternary; Protein Structure, Tertiary; Protein Subunits; Sequence Homology, Amino Acid; Solvents; Structure-Activity Relationship; Surface Properties
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/S0969-2126(02)00697-4

Collagen X is expressed specifically in the growth plate of long bones. Its C1q–like C–terminal NC1 domain forms a stable homotrimer and is crucial for collagen X assembly. Mutations in the NC1 domain cause Schmid metaphyseal chondrodysplasia (SMCD). The crystal structure at 2.0 Å resolution of the human collagen X NC1 domain reveals an intimate trimeric assembly strengthened by a buried cluster of calcium ions. Three strips of exposed aromatic residues on the surface of NC1 trimer are likely to be involved in the supramolecular assembly of collagen X. Most internal SMCD mutations probably prevent protein folding, whereas mutations of surface residues may affect the collagen X suprastructure in a dominant-negative manner.