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.
Zhang M, Abrams C, Wang L, Gizzi A, He L, Lin R, Chen Y, Loll PJ, Pascal JM, Zhang JF. Structural basis for calmodulin as a dynamic calcium sensor. Structure (Cell Press). 2012 May 9;20(5):911-23. PMCID: PMC3372094. doi: 10.1016/j.str.2012.03.019
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