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J Mol Biol. 2014 Jan 23;426(2):467-83. doi: 10.1016/j.jmb.2013.10.010. Epub 2013 Oct 10.

Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels.

Author information

1
Cardiovascular Research Institute, University of California, San Francisco, CA 94158-9001, USA.
2
Institut National de la Santé et de la Recherche Médicale, UMR 1087, F-44000 Nantes, France; Centre National de la Recherche Scientifique, UMR 6291, F-44000 Nantes, France; L'institut du thorax, L'UNAM, Université de Nantes, F-44000 Nantes, France.
3
Cardiovascular Research Institute, University of California, San Francisco, CA 94158-9001, USA; Departments of Biochemistry and Biophysics and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158-9001, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94158-9001, USA; Physical Biosciences Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: daniel.minor@ucsf.edu.

Abstract

Voltage-gated sodium channels (NaVs) are central elements of cellular excitation. Notwithstanding advances from recent bacterial NaV (BacNaV) structures, key questions about gating and ion selectivity remain. Here, we present a closed conformation of NaVAe1p, a pore-only BacNaV derived from NaVAe1, a BacNaV from the arsenite oxidizer Alkalilimnicola ehrlichei found in Mono Lake, California, that provides insight into both fundamental properties. The structure reveals a pore domain in which the pore-lining S6 helix connects to a helical cytoplasmic tail. Electrophysiological studies of full-length BacNaVs show that two elements defined by the NaVAe1p structure, an S6 activation gate position and the cytoplasmic tail "neck", are central to BacNaV gating. The structure also reveals the selectivity filter ion entry site, termed the "outer ion" site. Comparison with mammalian voltage-gated calcium channel (CaV) selectivity filters, together with functional studies, shows that this site forms a previously unknown determinant of CaV high-affinity calcium binding. Our findings underscore commonalities between BacNaVs and eukaryotic voltage-gated channels and provide a framework for understanding gating and ion permeation in this superfamily.

KEYWORDS:

DDM; EGTA; PD; PEG; VGIC; VSD; X-ray crystallography; electrophysiology; ethylene glycol-bis( 2-aminoethylether)-N, N,N′,N′-tetraacetic acid; ion binding; polyethylene glycol; pore domain; voltage-gated calcium channel; voltage-gated ion channel; voltage-gated sodium channel; voltage-sensing domain; β-dodecyl maltoside

PMID:
24120938
PMCID:
PMC3947372
DOI:
10.1016/j.jmb.2013.10.010
[Indexed for MEDLINE]
Free PMC Article

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