Cumulative hydropathic topology of a voltage-gated sodium channel at atomic resolution

Markos N. Xenakis, Dimos Kapetis, Yang Yang, Jordi Heijman, Stephen G. Waxman, Giuseppe Lauria, Catharina G. Faber, Hubert J. Smeets, Ronald L. Westra, Patrick J. Lindsey

Research output: Contribution to journalArticlepeer-review

Abstract

Voltage-gated sodium channels (NavChs) are biological pores that control the flow of sodium ions through the cell membrane. In humans, mutations in genes encoding NavChs can disrupt physiological cellular activity thus leading to a wide spectrum of diseases. Here, we present a topological connection between the functional architecture of a NavAb bacterial channel and accumulation of atomic hydropathicity around its pore. This connection is established via a scaling analysis methodology that elucidates how intrachannel hydropathic density variations translate into hydropathic dipole field configurations along the pore. Our findings suggest the existence of a nonrandom cumulative hydropathic topology that is organized parallel to the membrane surface so that pore's stability, as well as, gating behavior are guaranteed. Given the biophysical significance of the hydropathic effect, our study seeks to provide a computational framework for studying cumulative hydropathic topological properties of NavChs and pore-forming proteins in general.

Original languageEnglish
Pages (from-to)1319-1328
Number of pages10
JournalProteins: Structure, Function and Bioinformatics
Volume88
Issue number10
DOIs
Publication statusPublished - Oct 1 2020

Keywords

  • cumulative hydropathic effects
  • hydrophobic gating
  • NavAb
  • scaling
  • topology
  • voltage-gated sodium channels

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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