Elucidating Molecular Mechanisms of Protoxin-2 State-specific Binding to the Human Na_V1.7 Channel.

ABSTRACT: Human voltage-gated sodium (hNa_V) channels are responsible for initiating and propagating action potentials in excitable cells and mutations have been associated with numerous cardiac and neurological disorders. hNa_V1.7 channels are expressed in peripheral neurons and are promising targets for pain therapy. The tarantula venom peptide protoxin-2 (PTx2) has high selectivity for hNa_V1.7 and serves as a valuable scaffold to design novel therapeutics to treat pain. Here, we used computational modeling to study the molecular mechanisms of the state-dependent binding of PTx2 to hNa_V1.7 voltage-sensing domains (VSDs). Using Rosetta structural modeling methods, we constructed atomistic models of the hNa_V1.7 VSD II and IV in the activated and d

SUBMITTER: Ngo K 

PROVIDER: S-EPMC10002706 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature