The structure of the cytoplasmic domain of the chloride channel ClC-Ka reveals a conserved interaction interface.
The cytoplasmic domains of ClC chloride channels and transporters are ubiquitously found in eukaryotic family members and have been suggested to be involved in the regulation of ion transport. All cytoplasmic ClC domains share a conserved scaffold that contains a pair of CBS motifs. Here we describe the structure of the cytoplasmic component of the human chloride channel ClC-Ka at 1.6 A resolution. The structure reveals a dimeric organization of the domain that is unusual for CBS motif containing proteins. Using a biochemical approach combining mutagenesis, crosslinking, and analytical ultracentrifugation, we demonstrate that the interaction interface is preserved in solution and that the distantly related channel ClC-0 likely exhibits a similar structural organization. Our results reveal a conserved interaction interface that relates the cytoplasmic domains of ClC proteins and establish a structural relationship that is likely general for this important family of transport proteins.
Markovic
Sandra
S
Department of Biochemistry, University of Zürich, Winterthurer Strasse 190, CH-8057 Zürich, Switzerland.
Dutzler
Raimund
R
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018118:Chloride Channels / Q000737:chemistry* / Q000235:genetics; D017124:Conserved Sequence; D003593:Cytoplasm / Q000737:chemistry; D019281:Dimerization; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
C489932:CLCNKA protein, human; D018118:Chloride Channels