Molecular Recognition of Calmodulin in the Absence of Ca²⁺

Abstract

Ca²⁺-free calmodulin (apocalmodulin) binds target proteins and alters their function. Apocalmodulin has roles in the cell that apparently do not require the ability to bind Ca²⁺ at all, and these roles appear to be essential for cell's metabolism. Small-angle X-ray scattering (SAXS) results indicate that the overall conformation of apocalmodulin remains unchanged, but the conformation for the C-domain changes from the closed to semi-open conformation upon binding the target proteins. The conformational change would be induced by electrostatic interactions and subsequent van der Waals interactions and it can cause changes in the Ca²⁺ affinity of the apocalmodulin-target protein complex. An analysis of residue pairs between calmodulin and target peptides suggests that apocalmodulin recognizes Ca²⁺-dependent calmodulin binding proteins, utilizing a new motif different from IQ motif.