title: Deciphering voltage-gated Na(+) and Ca(2+) channels by studying prokaryotic ancestors.
abstract: Voltage-gated sodium channels (NaVs) and calcium channels (CaVs) are involved in electrical signaling, contraction, secretion, synaptic transmission, and other physiological processes activated in response to depolarization. Despite their physiological importance, the structures of these closely related proteins have remained elusive because of their size and complexity. Bacterial NaVs have structures analogous to a single domain of eukaryotic NaVs and CaVs and are their likely evolutionary ancestor. Here we review recent work that has led to new understanding of NaVs and CaVs through high-resolution structural studies of their prokaryotic ancestors. New insights into their voltage-dependent activation and inactivation, ion conductance, and ion selectivity provide realistic structural models for the function of these complex membrane proteins at the atomic level.
authors.affiliation: Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195, USA. Electronic address: wcatt@uw.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
authors.affiliation: Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Box 357280, University of Washington, Seattle, WA 98195, USA. Electronic address: nzheng@uw.edu.
authors.forename: Ning
authors.initials: N
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D061566:Voltage-Gated Sodium Channels
keywords: Na(V)Ab; NaChBac; selectivity filter; slow inactivation; voltage sensor; voltage-gated calcium channel; voltage-gated sodium channel