Fig. 7: Disease mutations mapping on NALCN and TTX incompatibility of NALCN.
From: Structure of the human sodium leak channel NALCN in complex with FAM155A
a Please also refer to Supplementary Table 3 for a summary of the disease-related mutations on human NALCN. The Cα atoms of the residues whose mutations lead to human diseases are mapped to the structure of NALCN and shown as spheres. The mapping is shown on both sides and extracellular views. b Superimposition of the pore helices and SF of NALCN with that of TTX-bound Nav1.7 (left). The determinant Tyr362 for TTX coordination in Nav1.7 is not conserved in NALCN and the structural deviations in the pore region of NALCN also result in potential clashes with the TTX binding site, making NALCN and TTX incompatible. As a comparison, despite lack of the determinant Tyr, TTX-insensitive Nav1.5 shows a similar backbone structure of pore helices and SF to that of TTX-bound Nav1.7, thus retains a lower binding affinity to TTX (right).
