A helical region in the C terminus of small-conductance Ca2+-activated K+ channels controls assembly with apo-calmodulin.
Small conductance Ca(2+)-activated potassium (SK) channels underlie the afterhyperpolarization that follows the action potential in many types of central neurons. SK channels are voltage-independent and gated solely by intracellular Ca(2+) in the submicromolar range. This high affinity for Ca(2+) results from Ca(2+)-independent association of the SK alpha-subunit with calmodulin (CaM), a property unique among the large family of potassium channels. Here we report the solution structure of the calmodulin binding domain (CaMBD, residues 396-487 in rat SK2) of SK channels using NMR spectroscopy. The CaMBD exhibits a helical region between residues 423-437, whereas the rest of the molecule lacks stable overall folding. Disruption of the helical domain abolishes constitutive association of CaMBD with Ca(2+)-free CaM, and results in SK channels that are no longer gated by Ca(2+). The results show that the Ca(2+)-independent CaM-CaMBD interaction, which is crucial for channel function, is at least in part determined by a region different in sequence and structure from other CaM-interacting proteins.
Wissmann
Ralph
R
Department of Physiology II, University of Tübingen, Ob dem Himmelreich 7, 72074 Tübingen, Germany.
Bildl
Wolfgang
W
Neumann
Heinz
H
Rivard
Andre F
AF
Klöcker
Nikolaj
N
Weitz
Dietmar
D
Schulte
Uwe
U
Adelman
John P
JP
Bentrop
Detlef
D
Fakler
Bernd
B
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D011487:Protein Conformation; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014981:Xenopus
D002147:Calmodulin; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D002118:Calcium