The structure of nhTMEM16. (A) Side view from the plane of the membrane. The cutaway surface of subunit a is colored pink, and the cutaway surface of subunit b is light blue. Within the cutaway surfaces, transmembrane helices are represented as cylinders colored violet (TMD1) to red (TMD10). The TMDs are numbered in subunit a but unlabeled in subunit b. Interfacial residues (http://www.ebi.ac.uk/pdbe/pisa/) between subunits a and b are shown as spheres (subunit a, magenta; subunit b, blue). The C terminus of each subunit (Ca and Cb of subunits a and b, respectively) extends to wrap around the N terminus (Na and Nb) of the other. Green spheres are activating Ca2+ ions. (B) View from the extracellular space showing the interface between subunits along TMD10 and the cytoplasmic end of TMD3. (C) nhTMEM16 B-factors. B-factors are represented as the color and thickness of the worms (from blue = 62 to red = 288). The cytosolic N and C termini show considerable disorder compared with the TMDs. (D) Surface representation of the hydrophilic aqueduct. The structure in A was rotated in the plane of the membrane 90°. Hydrophilic residues are cyan; hydrophobic residues are magenta. Amino acids corresponding to the scrambling domain identified in TMEM16F are colored tan. (E) Dimer cavities. The same view as in B. The surface is translucent to reveal underlying transmembrane helices shown as cylinders (TMD3–6 are numbered). The surface was constructed using only amino acids in transmembrane helices and is colored cyan for hydrophilic and magenta for hydrophobic. (F) The surface in E was rotated 25° to reveal the aqueduct.
