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.

Download full-text


Available from: Sheng Ye, Feb 19, 2015
1 Follower
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The stability and ion binding properties of the homo-tetrameric pore domain of a prokaryotic, voltage-gated sodium channel are studied by extensive all-atom molecular dynamics simulations, with the channel protein being embedded in a fully hydrated lipid bilayer. It is found that Na(+) ion presents in a mostly hydrated state inside the wide pore of the selectivity filter of the sodium channel, in sharp contrast to the nearly fully dehydrated state for K(+) ions in potassium channels. Our results also indicate that Na(+) ions make contact with only one or two out of the four polypeptide chains forming the selectivity filter, and surprisingly, the selectivity filter exhibits robust stability for various initial ion configurations even in the absence of ions. These findings are quite different from those in potassium channels. Furthermore, an electric field above 0.5V/nm is suggested to be able to induce Na(+) permeation through the selectivity filter.
    Biochimica et Biophysica Acta 06/2012; 1818(11):2529-35. DOI:10.1016/j.bbamem.2012.06.003 · 4.66 Impact Factor
  • Source
    • "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). "
    The Journal of General Physiology 05/2011; 137(5):415-26. DOI:10.1085/jgp.201010577 · 4.57 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The Na(+) and K(+) channels are essential to neural signaling, but our current knowledge at the atomic level is mainly limited to the conducting mechanism of K(+). Unlike a K(+) channel having four equivalent K(+)-binding sites in its selectivity filter, a NaK channel has a vestibule in the middle part of its selectivity filter, and can conduct both Na(+) and K(+) ions. However, the underlying mechanism for non-selective ion conduction in NaK remains elusive. Here we find four small grottos connecting with the vestibule of the NaK selectivity filter, which form a vestibule-grotto complex perpendicular to the filter pore with a few water molecules within it. It is shown that two or more of the water molecules coming to the vestibule to coordinate the cation are necessary for conducting both Na(+) and K(+) ions, while only one water molecule in the vestibule will obstruct ion permeation. Thus, the complex with the aid of interior water movement forms a dynamic hydration valve which is flexible in conveying different cations through the vestibule. Similar exquisite hydration valve mechanisms are expected to be utilized by other non-selective cation channels, and the results should shed new light on the importance of water in neural signaling.
    Biochimica et Biophysica Acta 04/2010; 1798(8):1474-9. DOI:10.1016/j.bbamem.2010.04.002 · 4.66 Impact Factor
Show more