Calcium Binding to Extracellular Matrix Proteins, Functional and Pathological Effects
Calcium concentrations in the extracellular space are 4 to 5 orders of magnitude larger than inside cells. These concentrations are highly controlled by a unique receptor system (Brown et al., 1995); Ward and Ricardi, this book; Brown et al., this book). Free calcium concentration in serum has been determined to be 1.2 mM, however, spatial and time-dependent fluctuations have been detected (for a review, see Maurer et al., 1996). Many different proteins in the extracellular space bind calcium ions and a variety of calcium-binding motifs have been identified in these proteins, e.g. the EF-hand motif, which is common in cytosolic proteins (Maurer et al., 1996). Calcium ions bound to extracellular proteins may serve various functions, but primarily stabilize protein structure which explains tight calcium binding (micromolar or smaller K D values). In addition, sites for weakly bound calcium ions may sense variations in extracellular calcium levels and may be involved in regulation (Maurer et al., 1996); (Koch et al., 1997). This chapter will focus on relevant findings concerning functional and pathological effects of calcium binding to two extracellular matrix proteins (fibrillin-1 and COMP) and the cell adhesion protein E-cadherin. Possible molecular mechanisms for these effects will be discussed as well.
KeywordsArthritis Codon Adenoma Cysteine Proline
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