A short motif in the C-terminus of mouse bestrophin 3 [corrected] inhibits its activation as a Cl channel.
Bestrophins are a new family of anion channels. Here, we examined the Cl channel activity of mBest4. Surprisingly, wild type mouse bestrophin-4 (mBest4) did not induce functional Cl channels when over-expressed in HEK293 cells. However, deletion of part of the C-terminus (residues 353-669) produced large Cl currents, suggesting the presence of a C-terminal motif that inhibited Cl channel function. Deletion of a short motif (356-364) or substitution of certain residues in this motif with alanines also resulted in expression of robust Cl currents. The channel activity of the mBest4 protein lacking the C-terminus (residues 353-669) was specifically inhibited by co-expression of C-terminal fragments of mBest4 having the inhibitory motif, suggesting that the C-terminal motif blocked mBest4 channel activity probably by interacting with the channel pore.
Qu
Zhiqiang
Z
Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, 615 Michael Street, 535 Whitehead Building, Atlanta, GA 30322-3030, USA. zqu@emory.edu
Cui
Yuanyuan
Y
Hartzell
Criss
C
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D004553:Electric Conductivity; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010539:Permeability; D017384:Sequence Deletion; D013861:Thiocyanates
D018118:Chloride Channels; D013861:Thiocyanates; D002118:Calcium