摘要
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Summary
Calmodulin is a prototypical and versatile Ca2+ sensor with EF hands as its high-affinity Ca2+ binding domains. Calmodulin is present in all eukaryotic cells, mediating Ca2+-dependent signaling. Upon binding Ca2+, calmodulin changes its conformation to form complexes with a diverse array of target proteins. Despite a wealth of knowledge on calmodulin, little is known on how target proteins regulate calmodulin's ability to bind Ca2+. Here, we take advantage of two splice variants of SK2 channels, which are activated by Ca2+-bound calmodulin but show different sensitivity to Ca2+ for their activation. Protein crystal structures and other experiments show that, depending on which SK2 splice variant it binds to, calmodulin adopts drastically different conformations with different affinities for Ca2+ at its C-lobe. Such target protein-induced conformational changes make calmodulin a dynamic Ca2+ sensor capable of responding to different Ca2+ concentrations in cellular Ca2+ signaling.
