Structure of human ClC-1.

(a) Overall topology of ClC-1 with 17 helices (αB to αR), 2 CBS domains, and key residues pinpointed. A single monomer is displayed for clarity. Helices are labelled with white letters throughout. (b) The 3.6 Å cryo-EM map (Map 0) from pH 7.5 covering the membrane domain only (contoured at σ = 13 in Pymol). Helix A (αA) and parts of the CBS domains were not resolved in the cryo-EM density maps. (c) Alternative cryo-EM map from pH 7.5 (Map 1) with the membrane and cytoplasmic CBS domains colored in cyan and red, respectively, shown at different contour levels (σ = 15 and 22 in Pymol, respectively). The map is filtered to 5 Å, representing the local resolution of the cytoplasmic domain (see also S2–S4 and S7 Figs). (d) Overall structure (generated using Map 1) with one of the monomers in pale colors. CBS, cystathionine-β-synthase; CLC, chloride channel; cryo-EM, cryo-electron microscopy.