A helical region in the C terminus of small-conductance Ca2+-activated K+ channels controls assembly with Apo-calmodulin

Ralph Wissmann, Wolfgang Bildl, Heinz Neumann, Andre F. Rivard, Nikolaj Klöcker, Dietmar Weitz, Uwe Schulte, John P. Adelman, Detlef Bentrop, Bernd Fakler

Research output: Contribution to journalArticle

34 Scopus citations

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 languageEnglish (US)
Pages (from-to)4558-4564
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number6
DOIs
StatePublished - Feb 8 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Wissmann, R., Bildl, W., Neumann, H., Rivard, A. F., Klöcker, N., Weitz, D., Schulte, U., Adelman, J. P., Bentrop, D., & Fakler, B. (2002). A helical region in the C terminus of small-conductance Ca2+-activated K+ channels controls assembly with Apo-calmodulin. Journal of Biological Chemistry, 277(6), 4558-4564. https://doi.org/10.1074/jbc.M109240200