Conformation and structural transitions in the EF-hands of calmodulin

Calcium plays a key role in cellular signal transduction. Calmodulin, a pro tein binding four calcium ions, is found in all eukaryotic cells and is bel ieved to activate such processes. The calcium binding loop found in this pr otein, the canonical EF-hand, is also found in a large number of other prot eins such as troponins, parvalbumins, calbindins etc. Earlier analysis of t he amino acid sequences of these proteins with a view of understanding evol ution of protein families and signaling mechanisms have provided extensive evidence for a characteristic double gene duplication event in this family of proteins. These analyses have been extended here to the three dimensiona l structures and the biophysical properties of the sequence segments of cal modulin EF-hands. The clear evolutionary history that shows up in sequences is not reflected as clearly in the conformation of individual EF-hands, wh ich may be a consequence of the much higher conservation pressure on the st ructure. Some evidence for the proposed gene duplication is implicit in the apo-holo structural transitions of the EF-hands. The profile of amino acid properties that might be significant for calcium binding, however, clearly reflects the gene duplication. These profiles might also provide insightfu l information on the calcium affinity of the EF-hand motifs and the nature of amino acid residues that constitute them.