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.

Download full-text


Available from: Sheng Ye, Feb 19, 2015
  • 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.
    Full-text · Article · Jun 2012 · Biochimica et Biophysica Acta
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ligand-gated ion channels couple the free energy of agonist binding to the gating of selective transmembrane ion pores, permitting cells to regulate ion flux in response to external chemical stimuli. However, the stereochemical mechanisms responsible for this coupling remain obscure. In the case of the ionotropic glutamate receptors (iGluRs), the modular nature of receptor subunits has facilitated structural analysis of the N-terminal domain (NTD), and of multiple conformations of the ligand-binding domain (LBD). Recently, the crystallographic structure of an antagonist-bound form of the receptor was determined. However, disulfide trapping of this conformation blocks channel opening, suggesting that channel activation involves additional quaternary packing arrangements. To explore the conformational space available to iGluR channels, we report here a second, clearly distinct domain architecture of homotetrameric, calcium-permeable AMPA receptors, determined by single-particle electron microscopy of untagged and fluorescently tagged constructs in a ligand-free state. It reveals a novel packing of NTD dimers, and a separation of LBD dimers across a central vestibule. In this arrangement, which reconciles diverse functional observations, agonist-induced cleft closure across LBD dimers can be converted into a twisting motion that provides a basis for receptor activation.
    Preview · Article · Jan 2012 · Frontiers in Molecular Neuroscience
  • 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). "

    Full-text · Article · May 2011 · The Journal of General Physiology
Show more