Selective ion permeation involves complexation with carboxylates and lysine in a model human sodium channel.

ABSTRACT: Bacterial and human voltage-gated sodium channels (Navs) exhibit similar cation selectivity, despite their distinct EEEE and DEKA selectivity filter signature sequences. Recent high-resolution structures for bacterial Navs have allowed us to learn about ion conduction mechanisms in these simpler homo-tetrameric channels, but our understanding of the function of their mammalian counterparts remains limited. To probe these conduction mechanisms, a model of the human Nav1.2 channel has been constructed by grafting residues of its selectivity filter and external vestibular region onto the bacterial NavRh channel with atomic-resolution structure. Multi-μs fully atomistic simulations capture long time-scale ion and protein movements associated with the permeation of Na+ and K+ ions, and their di

SUBMITTER: Flood E 

PROVIDER: S-EPMC6152994 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature