Abstract

The study of ion channels dates back to the 1950s and the groundbreaking electrophysiology work of Hodgin and Huxley, who used giant squid axons to probe how action potentials in neurons were initiated and propagated. More recently, several experiments using different structural biology techniques and approaches have been conducted to try to understand how potassium ions permeate through the selectivity filter of potassium ion channels. Two mechanisms of permeation have been proposed, and each of the two mechanisms is supported by different experiments. The key structural biology experiments conducted so far to try to understand how ion permeation takes place in potassium ion channels are reviewed and discussed. Protein crystallography has made, and continues to make, key contributions in this field, often through the use of anomalous scattering. Other structural biology techniques used to study the contents of the selectivity filter include solid-state nuclear magnetic resonance and two-dimensional infrared spectroscopy, both of which make clever use of isotopic labeling techniques, while molecular-dynamics simulations of ion flow through the selectivity filter have been enabled by the growing number of potassium ion channel structures deposited in the Protein Data Bank.

Highlights

  • The most abundant cation found in the cytoplasm of living things is the potassium ion

  • Perhaps the most important of these is the selectivity filter (SF), which is a narrow channel running through the protein that is formed at the meeting point of four subunits that make up a complete ion channel (Fig. 1b)

  • We focus on structural biology techniques, but many biochemical (Hoomann et al, 2013; Imai et al, 2010) and molecular-dynamics studies (Flood et al, 2019) have been conducted to measure ion and water flow through potassium ion channels

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Summary

Introduction

The most abundant cation found in the cytoplasm of living things is the potassium ion. Ion channels are often formed from four subunits with the SF found at their center For this reason, they often crystallize in tetragonal-based space groups, often with the four binding sites in the SF on a unit-cell axis (Zhou & MacKinnon, 2003; Alam & Jiang, 2009a). They often crystallize in tetragonal-based space groups, often with the four binding sites in the SF on a unit-cell axis (Zhou & MacKinnon, 2003; Alam & Jiang, 2009a) This means that all the atoms within the SF reside on special positions and have a maximum occupancy of 0.25. The key structural biology studies in this area are reviewed in order of publication from 2003 to 2019, with more studies expected in 2020 and the years beyond

Anomalous X-ray scattering studies of KcsA
Anomalous X-ray scattering from potassium ions
Solid-state nuclear magnetic resonance studies of the SF contents
Possible future studies
Conclusions
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