Calcium‐Binding Proteins

Abstract

Calcium ions act as critical second messengers in all eukaryotes and plants and are of fundamental importance to the normal development and functioning of all higher animal species. In mammals, calcium influences almost all aspects of cellular physiology and is particularly relevant for normal cardiac and neuronal function. Calcium signals are generated by the complex interplay of two opposing systems the first of which mediates calcium entry into the cell cytoplasm and a second clearance system that removes it. Exactly how these two systems integrate in space and time determines the precise nature of a given calcium signal. When the cytosolic calcium is elevated, it can be detected by a large number of diverse binding proteins, many of which decode specific signals into a biological output. According to well‐conserved structural elements, these proteins can be grouped into different families including annexins, C2 domain proteins and EF‐hand proteins. Key Concepts Calcium is an evolutionarily ancient and fundamental intracellular second messenger used by plants, animals and bacteria. Complex spatiotemporal calcium signals generated within cells are coupled to changes in biological activity. This is largely achieved through the presence of proteins that are able to rapidly bind Ca 2+ with high affinity These calcium‐binding proteins, or CaBPs, contain unique calcium chelating motifs formed by multiple amino acids in the protein primary sequence. Calcium binding to a CaBP can induce significant conformational rearrangements in the protein tertiary structure, which can expose binding sites for specific target interaction partners, thereby coupling the calcium signal to a unique cell signalling pathway. Calcium signalling events mediated by various CaBPs are becoming increasingly important as potential biomarkers and therapeutic targets for a range of human diseases.