An EF hand is a protein structural motif in which two alpha helices flank a loop. In a canonical calcium-binding EF hand, the loop contains 12 amino acid residues whose oxygen-containing groups organize a calcium ion site. PROSITE identifies coordinating positions 1, 3, 5, 7, 9 and 12; the final glutamate or aspartate can contribute two oxygen atoms. The motif is an arrangement of a chain, not a literal separate hand-shaped molecule.[ref]
EF-hand calcium-binding domain signature and profile in PROSITE. PDOC00018, Description: loop organization and coordinating positions
Structural evidence makes the arrangement concrete. The deposited calmodulin structure PDB 1CLL was determined by X-ray crystallography at resolution. Its model contains four calcium ions and two EF-hand binding loops in each lobe. A resolved ion and surrounding coordinates support a structural binding-site interpretation; they do not by themselves specify the rate or affinity of binding in every solution condition.[ref]
Calmodulin structure 1CLL in the Protein Data Bank. Experimental Data Snapshot and Primary Citation abstract
An original one-site model illustrates the distinction. If a site binds calcium independently with dissociation constant and free calcium concentration , the equilibrium occupied fraction isAt , half the sites are occupied; at , the fraction is . These values follow from the stipulated model and are not affinity measurements for PDB 1CLL.
EF hands commonly occur as interacting pairs, and atypical or altered relatives need not retain the same binding properties.[ref]
EF-hand calcium-binding domain signature and profile in PROSITE. Description: paired motifs, cooperativity and excluded nonbinding/atypical regions
Counting motifs alone therefore cannot justify treating every site as an identical independent binder. Structural arrangement, sequence chemistry and binding measurements provide complementary information. New to topics? Read the docs here!