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

Adam Lewis, Vilius Kurauskas, Marco Tonelli and Katherine Henzler-Wildman ()
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Adam Lewis: University of Wisconsin-Madison
Vilius Kurauskas: University of Wisconsin-Madison
Marco Tonelli: University of Wisconsin-Madison
Katherine Henzler-Wildman: University of Wisconsin-Madison

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26538-8

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DOI: 10.1038/s41467-021-26538-8

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