Article

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

Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA.
Nature (Impact Factor: 42.35). 04/2006; 440(7083):570-4. DOI: 10.1038/nature04508
Source: PubMed

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 perspective, 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 A and 2.8 A 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 nucleotide-gated channel and its structure may represent that of a cyclic nucleotide-gated channel pore.

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Available from: Sheng Ye, Feb 19, 2015
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    • "Molecular dynamics (MD) simulations show that K + conduction across the selectivity filter takes place by a concerted motion via the alternation of these two configurations [16]. In addition to the K + -selective channel, the crystal structures of another type of ion channels from Bacillus cereus called NaK that can conduct both Na + and K + ions were also reported [17] [18]. Based on these atomic structures, numerous computational studies were carried out to study the conduction, selectivity, and gating of the K + and NaK channels [15,16,19–30]. "
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    • "The critical role of the central region near the binding site S2 of KcsA is also reflected in the pore structure of homologous channels. For example, one of the main differences between the nonselective cationic NaK channel and the K + -selective KcsA channel is the widening of the pore at the level of the central binding site S2 in NaK (Shi et al., 2006). This led to the suggestion that loss of selectivity at the level of the central site S2 could be the principal reason why the NaK channel is able to conduct Na + unlike KcsA (Zagotta, 2006), which was correlated with MD simulations (Noskov and Roux, 2007). "
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    • "The basic MD model, generated with VMD [16], consists of the 2.8 Å resolution structure (PDB ID 2AHZ) of the K + -bound NaK [8] embedded in a fully hydrated dimyristoylphosphatidylcholine (DMPC) lipid bilayer, surrounded by a 200 mM KCl aqueous salt solution box. It contains totally 42,871 atoms, including 6900 protein atoms, 127 DMPC lipid molecules (67 and 60 in the extracellular and intracellular sides, respectively) with 14,986 atoms, 20,955 water atoms, 3 K + ions in the pore, at sites S1, S3 and in the cavity, respectively, and 6 K + and 21 Cl − ions in the bulk solution added randomly using the autoionize plugin of VMD. "
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