Structural basis for severe pain caused by mutations in the voltage sensors of sodium channel NaV1.7.

ABSTRACT: Voltage-gated sodium channels in peripheral nerves conduct nociceptive signals from nerve endings to the spinal cord. Mutations in voltage-gated sodium channel NaV1.7 are responsible for a number of severe inherited pain syndromes, including inherited erythromelalgia (IEM). Here, we describe the negative shifts in the voltage dependence of activation in the bacterial sodium channel NaVAb as a result of the incorporation of four different IEM mutations in the voltage sensor, which recapitulate the gain-of-function effects observed with these mutations in human NaV1.7. Crystal structures of NaVAb with these IEM mutations revealed that a mutation in the S1 segment of the voltage sensor facilitated the outward movement of S4 gating charges by widening the pathway for gating charge translocatio

SUBMITTER: Wisedchaisri G 

PROVIDER: S-EPMC10616507 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature