Sodium Ions Do Not Stabilize the Selectivity Filter of a Potassium Channel

Hendriks, Kitty; Öster, Carl; Shi, Chaowei; Sun, Han; Lange, Adam

doi:10.1016/j.jmb.2021.167091

Cited by 15 publications

(21 citation statements)

References 44 publications

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“…The data also indicate that several minor SF states exist in Na + . The CSPs we observe in the vicinity of the SF upon switching ion are largely consistent with very recent ssNMR data reported for NaK in liposomes 30 , further emphasizing that the structure and dynamics of NaK are essentially the same in bicelles and liposomes. To more precisely and quantitatively characterize the ion-dependent changes in SF structure and slow-timescale dynamics in the SF region and how the impact of ion binding propagates further down the NaK pore-lining helices, we turned to methyl NOESY and CPMG experiments.…”

Section: The Sf Conformation Is Ion-dependentsupporting

confidence: 90%

“…1). 13,30,37 Our observation of enhanced ps-ns dynamics for D66-S70 also explains the difficulty observing this region in ssNMR spectra. In line with the backbone flexibility, we observe extensive backbone CSPs in this region between K + and Na + -bound samples.…”

Section: Discussionmentioning

confidence: 58%

“…S1) and with the fact that correlations were not observed for residues 66-70 in dipolar-coupling based ssNMR experiments where structural heterogeneity impedes magnetization transfer. 13,30 Thus, our data clearly demonstrates that the extracellular mouth of the SF is structurally labile, potentially enabling this region to adapt to different types of bound ions.…”

Section: Nak Sf Flexibility Differs Markedly From the Intracellular To Extracellular Endmentioning

confidence: 67%

“…Recently reported ssNMR data supported ion-dependent structural changes in NaK solely in the vicinity of the SF. 30 In ssNMR spectra of NaK, resonances are not observed for residues 91-110, making it impossible to conclude how this region is affected by the permeant ion. Because we can resolve resonances throughout the NaK structure, we see that residues in the M2 helix show CSPs indicative of a structural change between the Na + -and K + -bound states.…”

Section: The M2 Helix Is Coupled To the Sfmentioning

confidence: 99%

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Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel

Lewis

Kurauskas

Tonelli

et al. 2021

Preprint

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The selectivity filter (SF) determines which ions are efficiently conducted through ion channel pores. NaK is a non-selective cation channel that conducts Na+ and K+ with equal efficiency. Crystal structures of NaK suggested a rigid SF structure, but later solid-state NMR and MD simulations questioned this interpretation. Here, we use solution NMR to characterize how bound Na+ vs. K+ affects NaK SF structure and dynamics. We find that the extracellular end of the SF is flexible on the ps-ns timescale regardless of bound ion. On a slower timescale, we observe a structural change between the Na+ and K+-bound states, accompanied by increased structural heterogeneity in Na+. We also show direct evidence that the SF structure is communicated to the pore via I88 on the M2 helix. These results support a dynamic SF with multiple conformations involved in non-selective conduction. Our data also demonstrate allosteric coupling between the SF and pore-lining helices in a non-selective cation channel that is analogous to the allosteric coupling previously demonstrated for K+-selective channels, supporting the generality of this model.

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Section: The Sf Conformation Is Ion-dependentsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 58%

Section: Nak Sf Flexibility Differs Markedly From the Intracellular To Extracellular Endmentioning

confidence: 67%

Section: The M2 Helix Is Coupled To the Sfmentioning

confidence: 99%

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Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel

Lewis

Kurauskas

Tonelli

et al. 2021

Preprint

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“…The previously discussed non-selective channel NaK can be made potassium-selective by two point mutations in the SF sequence from TVGDGN to TVGYGD or TVGFGD ( Alam and Jiang, 2009 ; Sauer et al, 2011 ). We have shown using ssNMR that these potassium-selective mutants lose their SF stability under sodium conditions and become disordered without stabilizing potassium ions ( Öster et al, 2019 ; Hendriks et al, 2021 ). The loss of SF stability strongly influences the hydrogen bonding network behind the SF and through this network impacts the pore helix ( Hendriks et al, 2021 ).…”

Section: Selectivity Filter Disordermentioning

confidence: 99%

Structural Plasticity of the Selectivity Filter in Cation Channels

2021

Self Cite

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Ion channels allow for the passage of ions across biological membranes, which is essential for the functioning of a cell. In pore loop channels the selectivity filter (SF) is a conserved sequence that forms a constriction with multiple ion binding sites. It is becoming increasingly clear that there are several conformations and dynamic states of the SF in cation channels. Here we outline specific modes of structural plasticity observed in the SFs of various pore loop channels: disorder, asymmetry, and collapse. We summarize the multiple atomic structures with varying SF conformations as well as asymmetric and more dynamic states that were discovered recently using structural biology, spectroscopic, and computational methods. Overall, we discuss here that structural plasticity within the SF is a key molecular determinant of ion channel gating behavior.

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