Potassium channels: structures, models, simulations

Abstract

Potassium channels have been studied intensively in terms of the relationship between molecular structure and physiological function. They provide an opportunity to integrate structural and computational studies in order to arrive at an atomic resolution description of mechanism. We review recent progress in K channel structural studies, focussing on the bacterial channel KcsA. Structural studies can be extended via use of computational (i.e. molecular simulation) approaches in order to provide a perspective on aspects of channel function such as permeation, selectivity, block and gating. Results from molecular dynamics simulations are shown to be in good agreement with recent structural studies of KcsA in terms of the interactions of K(+) ions with binding sites within the selectivity filter of the channel, and in revealing the importance of filter flexibility in channel function. We discuss how the KcsA structure may be used as a template for developing structural models of other families of K channels. Progress in this area is explored via two examples: inward rectifier (Kir) and voltage-gated (Kv) potassium channels. A brief account of structural studies of ancillary domains and subunits of K channels is provided.

Focus on Kir7.1: physiology and channelopathy

“…31,32 This stoichiometry was confirmed by velocity sedimentation with sucrose density gradients, size exclusion column chromatography, and chemical cross-linking. 33 A reference gene sequence (NG016742) spanning 111327-129090 of the original human BAC library clone RP11-174L18, constructed from chromosome 2 of a male blood DNA (AC064852) harbored the K ir 7.1 DNA sequence.…”

“…Immunoreactivity studies demonstrated the presence of Na C , K C -ATPase on the apical membrane of RPE and choroid plexus 32 and suggested the possible functional coupling with Kir7.1 in K C recycling (Fig. 2).…”

Acute Alcohol Tolerance Is Intrinsic to the BKCa Protein, but Is Modulated by the Lipid Environment

“…Cellular membranes contain lipid domains (lipid rafts) that are enriched in sphingomyelin and cholesterol and have different thickness (57) compared with the rest of membrane. Together with our increasing appreciation of ion channel structure and function (58), recent advances in the study of cell membrane organization are changing to reflect the broader functional role of the plasma membrane. The lipid bilayer not only provides a matrix for the membrane protein but also actively participates in signal transduction (by interacting with the protein) (41).…”

Trk2 Potassium Transport System in Streptococcus mutans and Its Role in Potassium Homeostasis, Biofilm Formation, and Stress Tolerance

“…Kch is a hypothetical protein in the S. mutans UA159 chromosome encoded by SMU_1848 (NCBI) with high homology to conserved ion channel-like domains of either two helices or a tetrameric structure and belongs to the family of pfam07885, which has a conserved GYG sequence shown to result in glycine-rich selectivity for K ϩ ions (33). Role of K ؉ in S. mutans.…”