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

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

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

Ion selectivity is one of the basic properties that define an ion channel. Most tetrameric cation channels, which include the K+, Ca 2+, 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 from Bacillus 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 an 86Rb 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 nucleotidegated channel and its structure may represent that of a cyclic nucleotide-gated channel pore.

Original languageEnglish (US)
Pages (from-to)570-574
Number of pages5
JournalNature
Volume440
Issue number7083
DOIs
StatePublished - Mar 23 2006
Externally publishedYes

Bibliographical note

Funding Information:
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.).

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