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Atomic structure of a Na+- and K+-conducting channel

Naturevolume 440, pages570–574 (2006)Cite this article

Abstract

Ion selectivity is one of the basic properties that define an ion channel. Most tetrameric cation channels, which include the K+, Ca2+, Na+ and cyclic nucleotide-gated channels, probably share a similar overall architecture in their ion-conduction pore, but the structural details that determine ion selection are different. Although K+ channel selectivity has been well studied from a structural perspective1,2, little is known about the structure of other cation channels. Here we present crystal structures of the NaK channel fromBacillus cereus, a non-selective tetrameric cation channel, in its Na+- and K+-bound states at 2.4 Å and 2.8 Å resolution, respectively. The NaK channel shares high sequence homology and a similar overall structure with the bacterial KcsA K+ channel, but its selectivity filter adopts a different architecture. Unlike a K+ channel selectivity filter, which contains four equivalent K+-binding sites, the selectivity filter of the NaK channel preserves the two cation-binding sites equivalent to sites 3 and 4 of a K+ channel, whereas the region corresponding to sites 1 and 2 of a K+ channel becomes a vestibule in which ions can diffuse but not bind specifically. Functional analysis using an86Rb flux assay shows that the NaK channel can conduct both Na+ and K+ ions. We conclude that the sequence of the NaK selectivity filter resembles that of a cyclic nucleotide-gated channel and its structure may represent that of a cyclic nucleotide-gated channel pore.

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Figure 1:Overall structure of NaK.
Figure 2:Structural comparison of the selectivity filters in NaK and KcsA.
Figure 3:Ion binding in the NaK channel.
Figure 4:86Rb flux assay.

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Acknowledgements

We thank R. MacKinnon for discussion and critical review of the manuscript. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the US Department of Energy, Office of Energy Research. We thank the beamline staff for assistance in data collection. This work was supported by grants from the David and Lucile Packard Foundation (to Y.J.) and the Searle Scholars Program (to Y.J.). Author Contributions S.Y. and A.A. contributed equally to this work. S.Y. helped with the structure determination and A.A. performed the86Rb flux assay.

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Authors and Affiliations

  1. Department of Physiology, University of Texas Southwestern Medical Center, Texas, 75390-9040, Dallas, USA

    Ning Shi, Sheng Ye, Amer Alam, Liping Chen & Youxing Jiang

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  1. Ning Shi

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Correspondence toYouxing Jiang.

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Competing interests

Atomic coordinates of the Na+ and K+ complexes of the NaK channel have been deposited in the Protein Data Bank with accession numbers of 2AHY and 2AHZ, respectively. Reprints and permissions information is available atnpg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Figure 1 and Supplementary Tables 1–2. Supplementary Figure 1 shows a partial sequence alignment of NaK, K+ and CNG channels. Supplementary Table 1 lists the data collection and refinement statistics. Supplementary Table S2 lists the statistical quantities for the data from those soaked crystals. (PDF 123 kb)

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Shi, N., Ye, S., Alam, A.et al. Atomic structure of a Na+- and K+-conducting channel.Nature440, 570–574 (2006). https://doi.org/10.1038/nature04508

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