Role of TRPM4 ion channel in pediatric arrhythmic syndromes

Figure 4 TRPM4 cryoEM structure. A: Extracellular view of the TRPM4 cryoEM structure (PDB ID: 5wp6). Four identical subunits are differently colored to highlight intersubunit contacts of the four R964 residues, which stabilize the folding of P-loops that harbor the channel selectivity-filter; arginine R964 in P-loop helix P1 and glycine G976 in the selectivity filter are shown by spherical atoms; B: Close-up views of 3D-aligned AlphaFold 3 (AF3) models of the wildtype channel TRPM4 (green) and R964S mutant channel (brown); mutation R964S eliminates the salt bridge that stabilizes an intersubunit contact between helix P1 and a linker connecting the selectivity filter and helix S6; C: Close-up view of the selectivity filter region in the AF3 models; elimination of the intersubunit contact (B) cases a noticeable widening of the selectivity-filter region that likely affects the ion selectivity of the channel.