EFhandcontaining

EF-hand containing refers to a broad class of calcium-binding proteins that share the EF-hand motif, a helix–loop–helix structural domain capable of binding calcium ions. The motif is typically composed of a loop of about 12 amino acids flanked by two alpha helices, commonly designated the E and F helices. In the loop, calcium coordination is achieved through several conserved ligands provided by side chains and backbone carbonyls; a characteristic calcium-binding signature, often including a DXDXDG-like motif, helps position ligands for Ca2+ binding. Many proteins harbor multiple EF-hand domains in tandem, allowing cooperative calcium binding and larger conformational changes.

Functionally, calcium binding to EF-hand motifs induces conformational rearrangements that regulate interactions with diverse targets, such as enzymes, ion channels, receptors, and cytoskeletal components. This enables roles in muscle contraction, neurotransmitter release, enzyme activity modulation, and signal transduction. EF-hand containing proteins thus act as calcium sensors or regulators, translating changes in intracellular Ca2+ into specific cellular responses.

Common examples include calmodulin, which contains four EF-hands and serves as a versatile calcium sensor; troponin C, a central regulator of muscle contraction; parvalbumin, a calcium buffer; the S100 family of acidic calcium-binding proteins; and recoverin, a neuronal calcium sensor. Beyond these, numerous other EF-hand containing proteins participate in diverse processes and are found throughout eukaryotes and in some prokaryotes.

Evolutionarily, the EF-hand motif has diversified through gene duplication and divergence, giving rise to proteins with varying numbers of EF-hands and target specificities. Abnormal EF-hand function or signaling is associated with various diseases, highlighting the motif’s central role in calcium-mediated regulation.