4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-26538-8

Keywords

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Funding

  1. NIGMS of the National Institutes of Health [R01GM116047, R35GM141748]
  2. NIH (NIGMS) [R24GM141526, P41GM103399]

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The selectivity filter (SF) in NaK is dynamic, with structural differences between Na+ and K+-bound states, determining efficient conduction of ions. The SF structure communicates with the pore-lining helices, supporting multiple conformations involved in non-selective conduction. Allosteric coupling between the SF and pore-lining helices is demonstrated, similar to that in K+-selective channels, indicating a general model for ion channel function.
NaK is a bacterial non-selective cation channel. Here, the authors use solution NMR to show that selectivity filter (SF) in NaK is dynamic, with structural differences between the Na+ and K + -bound states. The conformation of the SF is communicated to the pore-lining helices similarly as in the K + -selective channels. 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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