4.5 Article

Structural plasticity of the selectivity filter in a nonselective ion channel

Journal

IUCRJ
Volume 8, Issue -, Pages 421-430

Publisher

INT UNION CRYSTALLOGRAPHY
DOI: 10.1107/S205225252100213X

Keywords

ion channels; membrane proteins; X-ray crystallography; solid-state NMR; molecular dynamics

Funding

  1. Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy
  2. Office of Biological and Environmental Research
  3. US Department of Energy, Office of Biological and Environmental Research [DEAC02-06CH11357]
  4. German Research Foundation (DFG) [FOR 2518]
  5. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy [EXC 2008-390540038-UniSysCat]
  6. NIH [R01-GM071939]

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The crystallographic study of the sodium potassium ion channel (NaK) identified differences in conformation of the selectivity filter and inner helix among the four subunits forming the ion channel. The study also revealed a unique side-entry ion-conduction pathway for Na+ permeation in NaK. Additionally, NMR and molecular dynamics simulations confirmed the dynamic nature of the selectivity filter and inner helix, highlighting their importance in efficient ion conduction through the non-selective ion channel of NaK.
The sodium potassium ion channel (NaK) is a nonselective ion channel that conducts both sodium and potassium across the cellular membrane. A new crystallographic structure of NaK reveals conformational differences in the residues that make up the selectivity filter between the four subunits that form the ion channel and the inner helix of the ion channel. The crystallographic structure also identifies a side-entry, ion-conduction pathway for Na+ permeation that is unique to NaK. NMR studies and molecular dynamics simulations confirmed the dynamical nature of the top part of the selectivity filter and the inner helix in NaK as also observed in the crystal structure. Taken together, these results indicate that the structural plasticity of the selectivity filter combined with the dynamics of the inner helix of NaK are vital for the efficient conduction of different ions through the non-selective ion channel of NaK.

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