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.
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
Zhiqiang
Z
Qu
Yuanyuan
Y
Cui
Criss
C
Hartzell
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