PubMed 22579256

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: SK2

Title: Structural basis for calmodulin as a dynamic calcium sensor.

Authors: Miao Zhang, Cameron Abrams, Liping Wang, Anthony Gizzi, Liping He, Ruihe Lin, Yuan Chen, Patrick J Loll, John M Pascal, Ji-fang Zhang

Journal, date & volume: Structure, 2012 May 9 , 20, 911-23

PubMed link:

Calmodulin is a prototypical and versatile Ca(2+) sensor with EF hands as its high-affinity Ca(2+) binding domains. Calmodulin is present in all eukaryotic cells, mediating Ca(2+)-dependent signaling. Upon binding Ca(2+), 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 Ca(2+). Here, we take advantage of two splice variants of SK2 channels, which are activated by Ca(2+)-bound calmodulin but show different sensitivity to Ca(2+) 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 Ca(2+) at its C-lobe. Such target protein-induced conformational changes make calmodulin a dynamic Ca(2+) sensor capable of responding to different Ca(2+) concentrations in cellular Ca(2+) signaling.