Swapping of functional domains in voltage-gated K+ channels.
Functionally significant properties of domains in the amino acid sequence of potassium (K+) channel-forming proteins have been investigated by constructing chimeric K+ channels. The N-terminal domain of ShA2 channels was responsible for the fast inactivation (IKA) and also determined a shift in the threshold of activation whereas the membrane domain determined the timecourse of slow inactivation. The binding site for dendrotoxin (DTX), but not for mast cell degranulating peptide (MCDP), is completely located on the loop between the membrane spanning segments S5 and S6 in RCK1 channels. A certain part of this region which has recently been designated as a narrow part of the pore was found to be not responsible for the differences in the single-channel current amplitude between RCK4 and RCK2 K+ channels. Interchange of the C-terminal domain did not influence activation or inactivation of the channels.
Ruhr-Universität Bochum, Lehrstuhl für Biochemie, F.R.G.
M
M
Stocker
O
O
Pongs
M
M
Hoth
S H
SH
Heinemann
W
W
Stühmer
K H
KH
Schröter
J P
JP
Ruppersberg
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001514:Bee Venoms / Q000494:pharmacology; D002678:Chimera; D004247:DNA / Q000235:genetics; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009841:Oligonucleotides; D009865:Oocytes / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051381:Rats; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014714:Vertebrates; D014981:Xenopus
D001514:Bee Venoms; D004546:Elapid Venoms; D009841:Oligonucleotides; D010455:Peptides; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; C008331:mast cell degranulating peptide; D019789:Tetraethylammonium; C020273:dendrotoxin; D004247:DNA