Structural and functional aspects of calcium binding in extracellular matrix proteins.

Ca2+ ions play crucial roles in many matrix-matrix, cell-matrix and cell-cell contacts. Recent X-ray and NMR structure determinations have revealed an intriguing diversity of Ca(2+)-binding sites in extracellular proteins, ranging from the stabilization of isolated domains to intimate involvement in the superstructure of macromolecular assemblies. The central role of Ca2+ in extracellular proteins is illustrated by the molecular characterization of hereditary connective tissue disorders in humans. Point mutations of Ca(2+)-binding residues in fibrillin and cartilage oligomeric matrix protein are responsible for Marfan syndrome and pseudoachondroplasia, respectively. We also discuss the possibility that structure and function of extracellular proteins may be regulated by physiologically relevant Ca2+ gradients.