Fig. 3: Structure of TRPM7 with the gain-of-function mutation N1098Q.

a Superposition of TRPM7_Closed (green) and TRPM7-N1098Q_Open (yellow) structures. Only two of four subunits are shown, with the front and back subunits omitted for clarity. Pink arrows show domain movements. b Pore-forming domain of TRPM7-N1098Q_Open with the residues contributing to the pore lining shown as sticks. Only two of four subunits are shown, with the front and back subunits omitted for clarity. The pore profile is shown as a space-filling model (grey). The π-bulge in the middle of S6 is labeled. c Pore radius for TRPM7-N1098Q_Open (yellow) and TRPM7_Closed (green) calculated using HOLE. The vertical dashed line denotes the radius of a water molecule, 1.4 Å. d A snapshot of the MD simulated system with TRPM7 shown as yellow ribbons, lipid bilayer acyl chains in grey and hydrophilic head groups as sticks, water as a light blue continuum, and Na⁺ and Cl⁻ ions as magenta and green spheres, respectively. e Water occupancy of the TRPM7_Closed channel (blue surface) in MD simulations with no applied voltage. Residues lining the pore are shown in sticks. f Cumulative distribution of Na⁺ ions (magenta spheres) in the TRPM7_Closed channel MD simulations with no applied voltage. g Water occupancy of the TRPM7-N1098Q_open channel (blue surface) in MD simulations with no applied voltage. The hydroxyl groups of Y1085 residues (shown as dark blue surface) contribute to the permeation pathway. Residues lining the pore are shown in sticks. h Cumulative distribution of K⁺ ions (magenta spheres) in the TRPM7-N1098Q_open channel MD simulations under applied voltage.