Solution structure and function of the "tandem inactivation domain" of the neuronal A-type potassium channel Kv1.4.
Cumulative inactivation of voltage-gated (Kv) K(+) channels shapes the presynaptic action potential and determines timing and strength of synaptic transmission. Kv1.4 channels exhibit rapid "ball-and-chain"-type inactivation gating. Different from all other Kvalpha subunits, Kv1.4 harbors two inactivation domains at its N terminus. Here we report the solution structure and function of this "tandem inactivation domain" using NMR spectroscopy and patch clamp recordings. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, whereas ID2 (residues 40-50) is a 2.5-turn helix made up of small hydrophobic amino acids. Functional analysis suggests that only ID1 may work as a pore-occluding ball domain, whereas ID2 most likely acts as a "docking domain" that attaches ID1 to the cytoplasmic face of the channel. Deletion of ID2 slows inactivation considerably and largely impairs cumulative inactivation. Together, the concerted action of ID1 and ID2 may promote rapid inactivation of Kv1.4 that is crucial for the channel function in short term plasticity.
Wissmann
Ralph
R
Department of Physiology II, University of Freiburg, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany.
Bildl
Wolfgang
W
Oliver
Dominik
D
Beyermann
Michael
M
Kalbitzer
Hans-Robert
HR
Bentrop
Detlef
D
Fakler
Bernd
B
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D051665:Kv1.4 Potassium Channel; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017433:Protein Structure, Secondary; D012996:Solutions; D013329:Structure-Activity Relationship
D051665:Kv1.4 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012996:Solutions