title: NMR structure of inactivation gates from mammalian voltage-dependent potassium channels.
abstract: The electrical signalling properties of neurons originate largely from the gating properties of their ion channels. N-type inactivation of voltage-gated potassium (Kv) channels is the best-understood gating transition in ion channels, and occurs by a 'ball-and-chain' type mechanism. In this mechanism an N-terminal domain (inactivation gate), which is tethered to the cytoplasmic side of the channel protein by a protease-cleavable chain, binds to its receptor at the inner vestibule of the channel, thereby physically blocking the pore. Even when synthesized as a peptide, ball domains restore inactivation in Kv channels whose inactivation domains have been deleted. Using high-resolution nuclear magnetic resonance (NMR) spectroscopy, we analysed the three-dimensional structure of the ball peptides from two rapidly inactivating mammalian K. channels (Raw3 (Kv3.4) and RCK4 (Kv1.4)). The inactivation peptide of Raw3 (Raw3-IP) has a compact structure that exposes two phosphorylation sites and allows the formation of an intramolecular disulphide bridge between two spatially close cysteine residues. Raw3-IP exhibits a characteristic surface charge pattern with a positively charged, a hydrophobic, and a negatively charged region. The RCK4 inactivation peptide (RCK4-IP) shows a similar spatial distribution of charged and uncharged regions, but is more flexible and less ordered in its amino-terminal part.
authors.affiliation: Institute of Physiology, University of Tubingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Antz
authors.forename: M
authors.initials: M
authors.lastname: Geyer
authors.forename: B
authors.initials: B
authors.lastname: Fakler
authors.forename: M K
authors.initials: MK
authors.lastname: Schott
authors.forename: H R
authors.initials: HR
authors.lastname: Guy
authors.forename: R
authors.initials: R
authors.lastname: Frank
authors.forename: J P
authors.initials: JP
authors.lastname: Ruppersberg
authors.forename: H R
authors.initials: HR
authors.lastname: Kalbitzer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004563:Electrochemistry; D015640:Ion Channel Gating; D009682:Magnetic Resonance Spectroscopy; D008322:Mammals; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D010446:Peptide Fragments; D015221:Potassium Channels