Structure of a Prokaryotic Sodium Channel Pore Reveals Essential Gating Elements and an Outer Ion Binding Site Common to Eukaryotic Channels

JOURNAL OF MOLECULAR BIOLOGY

卷:426

Article

Shaya, David¹  Findeisen, Felix¹  Abderemane-Ali, Fayal^2,3,4  Arrigoni, Cristina¹  Wong, Stephanie¹  Nurva, Shailika Reddy¹  Loussouarn, Gildas^2,3,4  Minor, Daniel L., Jr.^1,5,6,7,8 

[1] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA

[2] Inst Natl Sante & Rech Med, UMR 1087, F-44000 Nantes, France

[3] CNRS, UMR 6291, F-44000 Nantes, France

[4] Univ Nantes, LUNAM, Inst Thorax, F-44000 Nantes, France

[5] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA

[6] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA

[7] Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, San Francisco, CA 94158 USA

[8] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Sci Div, Berkeley, CA 94720 USA

关键词: voltage-gated sodium channel;    X-ray crystallography;    electrophysiology;    ion binding;    voltage-gated calcium channel;   

DOI  :  10.1016/j.jmb.2013.10.010

来源: Elsevier

【 摘 要 】

Voltage-gated sodium channels (Nays) are central elements of cellular excitation. Notwithstanding advances from recent bacterial Na-v (BacNa(v)) structures, key questions about gating and ion selectivity remain. Here, we present a closed conformation of Na(v)Ae1p, a pore-only BacNav derived from Na(v)Ae1, a BacNa(v) 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 BacNa(v)s 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 (Ca-v) 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. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

【 授权许可】

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