Cooperative subunit interactions in C-type inactivation of K channels.
C-type inactivation of potassium channels is distinct from N-terminal mediated (N-type) inactivation and involves a closing of the outer mouth of the channel. We have investigated the role of the individual subunits of the tetrameric channel in the C-type inactivation conformational change by comparing the inactivation rates of channels constructed from different combinations of subunits. The relationship between the inactivation rate and the number of fast subunits is exponential, as would be predicted by a cooperative mechanism where the C-type conformational change involves all four subunits, and rules out a mechanism where a conformational change in any of the individual subunits is sufficient for inactivation. Subunit interactions in C-type inactivation are further supported by an interaction between separate mutations affecting C-type inactivation when in either the same or separate subunits.
Ogielska
E M
EM
Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305, USA.
Zagotta
W N
WN
Hoshi
T
T
Heinemann
S H
SH
Haab
J
J
Aldrich
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D046911:Macromolecular Substances; D008433:Mathematics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D017354:Point Mutation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D051637:Shaker Superfamily of Potassium Channels; D013816:Thermodynamics; D014982:Xenopus laevis
D029721:Drosophila Proteins; D046911:Macromolecular Substances; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011994:Recombinant Proteins; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels