Figure 6.
Molecular model of the interaction between Pn3a and NaV1.7 VSDII down state. (A) Two cross-membrane views (180° rotated) of the interaction between the VSDII of Nav1.7 (green) and Pn3a (blue). The position of the lipid bilayer is indicated in olive green. (B) View parallel to the membrane showing the interaction of K22 and K24 with counter charges D816 and E818 in the S3–S4 segment. Only the side chains of selected residues are represented as sticks to increase readability. Hydrogen bonds that are discussed in the text are indicated by dashed lines. The VSDII is made of four α-helices noted as S1–S4. The molecular models were generated by homology using three templates: the cryo-EM structure of hNav1.7 VSDII-NaVAb chimera in complex with ProTx-II (PDB 6N4R), the cryo-EM structure of hNav1.7 (PDB 6J8H), and the NMR solution structure of Pn3a (PDB 5T4R).