Über altisländische Berserkergeschichten

von Hermann GuentertProgr. Nr. 86

Solution structure and fluctuation of the Mg2+-bound form of calmodulin C-terminal domain

Calmodulin (CaM) is a Ca2+-binding protein that functions as a ubiquitous Ca2+-signaling molecule, through conformational changes from the “closed” apo conformation to the “open” Ca2+-bound conformation. Mg2+ also binds to CaM and stabilizes its folded structure, but the NMR signals are broadened by slow conformational fluctuations. Using the E104D/E140D mutant, designed to decrease the signal broadening in the presence of Mg2+ with minimal perturbations of the overall structure, the solution structure of the Mg2+-bound form of the CaM C-terminal domain was determined by multidimensional NMR spectroscopy. The Mg2+-induced conformational change mainly occurred in EF hand IV, while EF-hand III retained the apo structure. The helix G and helix H sides of the binding sequence undergo conformational changes needed for the Mg2+ coordination, and thus the helices tilt slightly. The aromatic rings on helix H move to form a new cluster of aromatic rings in the hydrophobic core. Although helix G tilts slightly to the open orientation, the closed conformation is maintained. The fact that the Mg2+-induced conformational changes in EF-hand IV and the hydrophobic core are also seen upon Ca2+ binding suggests that the Ca2+-induced conformational changes can be divided into two categories, those specific to Ca2+ and those common to Ca2+ and Mg2+