Intracellular Calcium-Binding Proteins in Signal Transduction

Abstract

Cell stimulation generates a Ca²+ signal, which is perceived by intracellular Ca²⁺-binding proteins. These proteins are made up of different units of a conserved structural motif, called the 2S domain, and composed mainly of four β-helices and two anti parallel β-strands. This 2S domain can bind 2 Ca²⁺ ions and is roughly cup-shaped in the Ca²⁺-bound configuration. The interior of the cup is lined with solvent-exposed hydrophobic residues. In Ca²⁺-binding proteins involved in cellular signal-response coupling, such as calmodulin and troponin C, the hydrophobic cup is essential for interaction with, and activation of the response proteins. The Ca²⁺-free state is characterized by a reorientation of the β-helices and shielding of the hydrophobic residues in the cup. In contrast, interaction with the target strongly stabilizes the hydrophobic cups. Ca²⁺-buffering proteins, such as parvalbumin and sarcoplasmic Ca²⁺-binding proteins, have intrinsically a stable conformation, since the strongly hydrophobic cups are stabilized by frontal self association of the 2S domains.