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

Shaya D, Findeisen F, Abderemane-Ali F, Arrigoni C, Wong S, Nurva SR, Loussouarn G, Minor DL
J Mol Biol 426 467-83 (2014)
Related entries: 4lto, 4ltp, 4ltr

Cited: 86 times
EuropePMC logo PMID: 24120938

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.

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  1. Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels. Shaya D, Findeisen F, Abderemane-Ali F, Arrigoni C, Wong S, Nurva SR, Loussouarn G, Minor DL. J Mol Biol 426 467-483 (2014)


Reviews citing this publication (25)

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  9. Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart. Payandeh J, Minor DL. J Mol Biol 427 3-30 (2015)
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  18. Global versus local mechanisms of temperature sensing in ion channels. Arrigoni C, Minor DL. Pflugers Arch 470 733-744 (2018)
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  20. Voltage-gated Sodium Channels and Blockers: An Overview and Where Will They Go? Li ZM, Chen LX, Li H. Curr Med Sci 39 863-873 (2019)
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  23. Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets? Dalhoff A. Infection 49 569-589 (2021)
  24. Cav2.3 channel function and Zn2+-induced modulation: potential mechanisms and (patho)physiological relevance. Neumaier F, Schneider T, Albanna W. Channels (Austin) 14 362-379 (2020)
  25. The unique structural characteristics of the Kir 7.1 inward rectifier potassium channel: a novel player in energy homeostasis control. Hernandez CC, Gimenez LE, Dahir NS, Peisley A, Cone RD. Am J Physiol Cell Physiol 324 C694-C706 (2023)

Articles citing this publication (60)



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