(a) Single-subunit superposition of apo form and Mamba1-bound hASIC1aΔC shows global conformational changes. The domains of apo-hASIC1aΔC are shown in different colors, and Mamba1-bound hASIC1aΔC is colored grey. (b, c) Conformational changes in the acidic pocket and TMD of hASIC1aΔC upon Mamba1 binding. (b) View of the acidic pocket from superposed apo- and Mamba1-bound hASIC1aΔC. hASIC1aΔC is shown in cartoon representation and colored as in (a). Cα atoms of Glu238 and Asp347, Asp239 and Asp351 are shown as spheres. (c) View of the TMD from superposed apo- and Mamba1-bound hASIC1aΔC. The TMDs of hASIC1aΔC and the hASIC1aΔC-Mamba1 complex are shown as ribbons in red and grey, respectively. (d) Pore profiles of hASIC1aΔC (left) and the hASIC1aΔC-Mamba1 complex (right) calculated with HOLE software (red <1.4 Å<green < 2.3 Å<blue). (e) Plot of pore radius for the apo-form hASIC1aΔC (black, solid line), hASIC1aΔC-Mamba1 complex (red, solid line), cASIC1 in resting state (grey, dash line, PDB 6AVE), and cASIC1 in open state (blue, dash line, PDB 4NTW) along the threefold molecular axis.