Medicine and Health Sciences Commons^™

Structural Basis For Calmodulin As A Dynamic Calcium Sensor, Miao Zhang, Cameron Abrams, Liping Wang, Anthony Gizzi, Liping He, Ruihe Lin, Yuan Chen, Patrick J. Loll, John M. Pascal, Ji-Fang Zhang

Pharmacy Faculty Articles and Research

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 …