Evolution of EF-Hand Proteins

Abstract

EF-hand proteins are homologous; they have all evolved from a common precursor. They contain from two to twelve copies of the EF-hand domain. The EF-hand is about thirty amino acids long and consists of an α-helix (E), loop, and second α-helix (F). Usually a Ca²⁺ ion is bound in the loop under physiological conditions; however, 30% of all known EF-hands do not bind calcium. With only a few exceptions all EF-hand-containing proteins are found in the cytosols of eukaryotic cells. Most of them function as transducers of information. In so-called quiescent cells the concentration of the free Ca²⁺ ion is about 10^−7.2 M; following a stimulus to the cell [Ca²⁺] rises to ∼10^−5.8 M. Many EF-hand proteins are calcium modulated. In a quiescent cell they are in the apo or in the magnesium form; following stimulation they are in the calcium form. These calcium signals are tuned by complex spatial and temporal distributions, as well as by differing affinities and binding rates of calcium-modulated proteins. The focus of this review is to summarize the characteristics of the 66 known subfamilies of EF-hand proteins and to suggest general patterns of their evolution.