| Popis: |
Transient changes in the intracellular Ca2+ concentration play an important role in triggering signal transduction pathways. Depending on the stimulus and mode of Ca2+ entry into the cytosol, distinct signaling pathways (e. g. via Ca2+/calmodulin-dependent kinase and phosphatase, cAMP-dependent protein kinase A or protein kinase C) are chosen, leading to activation or inactivation of various enzymes and alterations in gene expression through distinct DNA regulatory elements (Bading et al1993; Jain et al, 1993; Peunova and Enikolopov, 1993). Many of the Ca2+-dependent cellular functions are mediated by cytosolic Ca2+-binding proteins which are known to influence Ca2+ levels and/or mediate Ca2+ signals within the cell (for a review, see Carafoli, 1987). Most of these proteins belong to a homologous class of small, acidic proteins, which constitute the superfamily of EF-hand type helix-loop-helix Ca2+-binding proteins. Over 260 members of this family have been discovered so far (for reviews, see Moncrief et al, 1990; Nakayama et al, 1992; Nakayama and Kretsinger, 1993). They all share as a common structural motif a Ca2+-binding loop which is flanked by two perpendicularly oriented a-helices (Fig. 1). Based on the crystal structure of parvalbumin (Fig. 2), which was the first Ca2+-binding protein to be crystallized, this structure was named the “EF-hand” after the C-terminal E-helix-loop-F-helix Ca2+-binding domain in this protein (Kretsinger and Nockolds, 1973). The Ca2+-binding motif enables reversible binding of Ca2+ with dissociation constants in the submicromlar to micromolar range (0.01 −10 μM), i.e at Ca2+ concentrations as found in the cytoplasm under resting conditions and after stimulation of the cell. |
