Molecular mechanism of the calcium‐induced conformational change in the spectrin EF‐hands.

Calcium is a universally employed cytosolic messenger in eukaryotic cells. Most of the proteins that bind signalling calcium are members of the calmodulin superfamily and share two or more helix‐loop‐helix motifs known as EF‐hands. A model, based on structure comparison of different domains and supported by preliminary NMR data, has suggested that EF‐hands involved in signal transduction undergo a major conformational change upon calcium binding from a ‘closed’ to an ‘open’ state allowing protein‐protein interaction. We have determined the solution structures of the EF‐hand pair from alpha‐spectrin in the absence and in the presence of calcium. The structures are in the closed and open conformation respectively, providing a definite experimental proof for the closed‐to‐open model. Our results allow formulation of the rules which govern the movement induced by calcium. These rules may be generalized to other EF‐hands since the key residues involved are conserved within the calmodulin family.