title: Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin.
abstract: Small-conductance Ca2+-activated K+ channels (SK channels) are independent of voltage and gated solely by intracellular Ca2+. These membrane channels are heteromeric complexes that comprise pore-forming alpha-subunits and the Ca2+-binding protein calmodulin (CaM). CaM binds to the SK channel through the CaM-binding domain (CaMBD), which is located in an intracellular region of the alpha-subunit immediately carboxy-terminal to the pore. Channel opening is triggered when Ca2+ binds the EF hands in the N-lobe of CaM. Here we report the 1.60 A crystal structure of the SK channel CaMBD/Ca2+/CaM complex. The CaMBD forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three alpha-helices, two from one CaMBD subunit and one from the other. As only the CaM N-lobe has bound Ca2+, the structure provides a view of both calcium-dependent and -independent CaM/protein interactions. Together with biochemical data, the structure suggests a possible gating mechanism for the SK channel.
authors.affiliation: Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA. schumacm@ohsu.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Schumacher
authors.forename: A F
authors.initials: AF
authors.lastname: Rivard
authors.forename: H P
authors.initials: HP
authors.lastname: Bächinger
authors.forename: J P
authors.initials: JP
authors.lastname: Adelman
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D015640:Ion Channel Gating; D008958:Models, Molecular; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels
chemical_list: D002147:Calmodulin; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels