Abstract
Small conductance Ca2+-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 Ca2+ in the submicromolar range. This high affinity for Ca2+ results from Ca2+-independent association of the SK α-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 Ca2+ free CaM, and results in SK channels that are no longer gated by Ca2+. The results show that the Ca2+-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.
Original language | English (US) |
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Pages (from-to) | 4558-4564 |
Number of pages | 7 |
Journal | Journal of Biological Chemistry |
Volume | 277 |
Issue number | 6 |
DOIs | |
State | Published - Feb 8 2002 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology