Molecular determinants of μ-conotoxin KIIIA interaction with the human voltage-gated sodium channel Na_V1.7.

ABSTRACT: The voltage-gated sodium (Na_V) channel subtype Na_V1.7 plays a critical role in pain signaling, making it an important drug target. Here we studied the molecular interactions between μ-Conotoxin KIIIA (KIIIA) and the human Na_V1.7 channel (hNa_V1.7). We developed a structural model of hNa_V1.7 using Rosetta computational modeling and performed in silico docking of KIIIA using RosettaDock to predict residues forming specific pairwise contacts between KIIIA and hNa_V1.7. We experimentally validated these contacts using mutant cycle analysis. Comparison between our KIIIA-hNa_V1.7 model and the cryo-EM structure of KIIIA-hNa_V1.2 revealed key similarities and differences between Na_V channel subty

SUBMITTER: Kimball IH 

PROVIDER: S-EPMC10060530 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature