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: 41.46). 04/2006; 440(7083):570-4. DOI: 10.1038/nature04508
Source: PubMed


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.


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 NaK channel is a member of a family that shares sequence similarity with TM1, TM2, and the pore loop of the AMPAR (Wo and Oswald, 1995; Panchenko et al., 2001; Kuner et al., 2003). It been crystallized in both the closed and open channel conformations (PDB entries 2AHY and 3E86, respectively; Shi et al., 2006; Alam and Jiang, 2009). As a result, we can compare the channel opening trajectories of the TM1 and TM2 attachment points to the corresponding trajectories of the LBD connection points C1 and C2. "
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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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