title: Structural basis for calmodulin as a dynamic calcium sensor.
abstract: 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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Jefferson Medical College, Philadelphia, PA 19107, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.forename: Cameron
authors.initials: C
authors.lastname: Abrams
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Gizzi
authors.forename: Liping
authors.initials: L
authors.lastname: He
authors.forename: Ruihe
authors.initials: R
authors.lastname: Lin
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Loll
authors.forename: John M
authors.initials: JM
authors.lastname: Pascal
authors.forename: Ji-fang
authors.initials: JF
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D015398:Signal Transduction; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002147:Calmodulin; D051640:Small-Conductance Calcium-Activated Potassium Channels; D002118:Calcium