NMR Structure of the “Ball-and-chain” Domain of KCNMB2, the β2-Subunit of Large Conductance Ca2+- and Voltage-activated Potassium Channels* 210

The auxiliary β-subunit KCNMB2 (β2) endows the non-inactivating large conductance Ca2+- and voltage-dependent potassium (BK) channel with fast inactivation. This process is mediated by the N terminus of KCNMB2 and closely resembles the “ball-and-chain”-type inactivation observed in voltage-gated potassium channels. Here we investigated the solution structure and function of the KCNMB2 N terminus (amino acids 1–45, BKβ2N) using NMR spectroscopy and patch clamp recordings. BKβ2N completely inactivated BK channels when applied to the cytoplasmic side; its interaction with the BK α-subunit is characterized by a particularly slow dissociation rate and an affinity in the upper nanomolar range. The BKβ2N structure comprises two domains connected by a flexible linker: the pore-blocking “ball domain” (formed by residues 1–17) and the “chain domain” (between residues 20–45) linking it to the membrane segment of KCNMB2. The ball domain is made up of a flexible N terminus anchored at a well ordered loop-helix motif. The chain domain consists of a 4-turn helix with an unfolded linker at its C terminus. These structural properties explain the functional characteristics of BKβ2N-mediated inactivation.

• Publication year

  2001

• Venue

  Journal of Biological Chemistry

• Publication date

  2001-11-09

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M107118200PMID 11517232
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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