Fig. 1: Cryo-EM structures and electrophysiological characterizations of human TMEM120A and TMEM120B.

a Cryo-EM maps of human TMEM120A and TMEM120B shown in two perpendicular views. Densities for the detergent micelle were omitted for visual clarity. The maps were contoured at level 0.7 and 0.6 for TMEM120A and TMEM120B in ChimeraX⁹, respectively. The dimer interfaces that are highlighted in the boxes are illustrated in detail in d with corresponding color borders. b TMEM120A and TMEM120B share nearly identical overall structure. TMEM120A and TMEM120B are colored cyan and yellow, respectively. c Structural topology of TMEM120A. One protomer is colored gray and the other is colored rainbow with the N- and C-terminus in blue and red, respectively. TMD, transmembrane domain; CCD, coiled coil domain. d Close-up views of the dimeric interfaces of TMD (left) and CCD (right). The TMD interfaces are along the C2 symmetry axis, which is indicated by the gray dashed lines. The C2 symmetry axis in the CCD is indicated by the circle in the upper panel. e Representative traces of poking-evoked whole-cell currents from HEK293T-P1KO cells transfected with mPiezo1 and TMEM120A, or from HEK293T cells transfected with TMEM120B and vector. f Statistic plot of the poking-evoked currents along the increase of indentation depth. g Representative traces of stretch-induced currents in a cell-attached mode from HEK293T-P1KO cells transfected with hPiezo1, TMEM120A, and vector. The stretch durations are indicated by red bars. h Statistic plot of the stretch-induced currents along the increase of negative pressure. i Structural comparison between TMEM120A and ELOVL7 elongase (PDB: 6Y7F), shown as cylindrical helices in two perpendicular views. The 3-keto acyl-CoA bound in ELOVL7 is shown as sticks. j Close-up view of the superimposition near the HxxHH motif in the catalytic site of ELOVL7. k A stretch of electron density is identified in the intracellular pocket of TMEM120A, which is surrounded by positively charged residues. The density is contoured at 4σ. Structure figures were prepared in PyMOL¹⁰.