Hydrophobic interface between two regulators of K+ conductance domains critical for calcium-dependent activation of large conductance Ca2+-activated K+ channels.
It has been suggested that the large conductance Ca(2)+-activated K(+) channel contains one or more domains known as regulators of K(+) conductance (RCK) in its cytosolic C terminus. Here, we show that the second RCK domain (RCK2) is functionally important and that it forms a heterodimer with RCK1 via a hydrophobic interface. Mutant channels lacking RCK2 are nonfunctional despite their tetramerization and surface expression. The hydrophobic residues that are expected to form an interface between RCK1 and RCK2, based on the crystal structure of the bacterial MthK channel, are well conserved, and the interactions of these residues were confirmed by mutant cycle analysis. The hydrophobic interaction appears to be critical for the Ca(2+)-dependent gating of the large conductance Ca(2+)-activated K(+) channel.
Kim
Hyun-Ju
HJ
Department of Life Science and Research Center for Biomolecular Nanotechnology, Gwangju Institute of Science and Technology, 1 Oryong-dong, Buk-gu, Gwangju 500-712, Korea.
Lim
Hyun-Ho
HH
Rho
Seong-Hwan
SH
Eom
Soo Hyun
SH
Park
Chul-Seung
CS
D000595:Amino Acid Sequence; D000818:Animals; D001704:Biopolymers / Q000378:metabolism; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D001704:Biopolymers; D024681:Potassium Channels, Calcium-Activated; D011188:Potassium; D002118:Calcium