EFhands

EF-hand is a calcium-binding structural motif found in a wide range of proteins. The name derives from the two helices that flank the calcium-binding loop, labeled E and F in the protein structure.

An EF-hand motif consists of a short helix–loop–helix element. The loop is about 12 residues long and coordinates a Ca2+ ion with six ligand positions supplied by side-chain oxygens and backbone carbonyls. Binding typically induces a conformational change in the surrounding helices, altering the protein’s surface properties and interaction potential.

Proteins bearing EF-hands include calmodulin, troponin C, parvalbumin, and members of the S100 family. They often function as calcium sensors or buffers, translating Ca2+ signals into interactions with target proteins. Many EF-hand proteins contain multiple motifs arranged in tandem, producing four-, six-, or eight-EF-hand domains.

Some EF-hands bind Mg2+ or are nonfunctional; evolutionary changes have yielded EF-hand–like domains with altered loops. The EF-hand superfamily is widespread in eukaryotes and underpins diverse calcium-dependent processes, from muscle regulation to enzyme activity and transcriptional control.