Extended Data Figure 6 : Structural features of the CLC-K channel.

From: Structure of a CLC chloride ion channel by cryo-electron microscopy

Extended Data Figure 6

a, Comparison between the CLC-K (class 1; grey and magenta) and EcCLC (yellow) structures. The TM domain of an EcCLC monomer was superposed onto that of CLC-K. α-Helices are represented as cylinders. b, The density of the extracellular loops αI–J of the CLC-K channel (class 1) is shown in blue and orange. The density of the remaining parts is shown in pale blue and yellow. In the top right panel, the model of one subunit is shown in the ribbon representation. αN and αF are highlighted, and Val166 and Tyr520 are shown in a ball-and-stick representation (green). The two ends of the αI–J link are indicated as cyan spheres with amino acid positions. The bottom panels show side views of one subunit with the αI–J link in blue density. The density map (5σ cut-off) was sharpened with a B-factor of −100 Å2 and low-pass filtered at 4.0 Å. c, As in the top left panel of b, but additionally showing a model of the αI–J link of EcCLC in a ball-and-stick representation (yellow). d, The same view as in the bottom right panel of b, but with superposition of an EcCLC model (pink; PDB accession 1OTS) onto the CLC-K model. A model for the αI–J linker of EcCLC is shown in yellow balls and sticks. e, Sequence alignment of the extracellular segments between TM helices αK and αM from various CLC proteins. The segments forming α-helices in the extracellular domain of bovine CLC-K are indicated by red coils. Red and blue dots indicate positions of mutations causing Bartter syndrome (CLC-Kb) and myotonia congenita (CLC-1), respectively. The A349D (ref. 5) mutation in CLC-Kb causes Bartter syndrome. The P408A (ref. 72), Q412P (ref. 73), F413C (ref. 4), A415V (ref. 74), E417G (ref. 75) or W433R (ref. 76) mutations in CLC-1 (corresponding to positions 342, 346, 347, 349, 351 and 367 of CLC-K, respectively) cause myotonia congenita. In addition, mutations at R438 (R438C in CLC-Kb or R496S in CLC-1), of which the side chain directly interacts with W367 (W433 in CLC-1) cause Bartter syndrome5 or myotonia congenita77 (see Fig. 4c).