Fig. 6.

Cryo-EM structure reveals a closed scramblase conformation of TMEM16K. a Structure of TMEM16K in 430 nM Ca²⁺ obtained by cryo-EM. Structural elements are coloured and viewed as in Fig. 2a. b Scaffold (red), TM4-6/α10^B (orange) and NCD/α7-α8 regions (blue) mapped onto the monomer fold as derived from domain motion analysis. c, d Relative motions of c the TM4-6/α10^B region (orange) and d the NCD/α7-α8 region, with the domains from the open groove crystal (dark colours) and closed groove 430 nM Ca²⁺ cryo-EM (lighter colours) structures viewed looking onto the c dimer interface and d scramblase groove. e−h Schematic representation of the scramblase groove in the crystal structure (e, g) and 430 nM Ca²⁺ structure (f, h). The groove is viewed perpendicular to the membrane normal (e, f) and from the ER luminal face (g, h). Pale green dotted surface represents the groove/channel profile as calculated by HOLE⁷⁷