Prokaryotic K⁺channels: From crystal structures to diversity

Abstract

The deep roots and wide branches of the K(+)-channel family are evident from genome surveys and laboratory experimentation. K(+)-channel genes are widespread and found in nearly all the free-living bacteria, archaea and eukarya. The conservation of basic structures and mechanisms such as the K(+) filter, the gate, and some of the gate's regulatory domains have allowed general insights on animal K(+) channels to be gained from crystal structures of prokaryotic channels. Since microbes are the great majority of life's diversity, it is not surprising that microbial genomes reveal structural motifs beyond those found in animals. There are open-reading frames that encode K(+)-channel subunits with unconventional filter sequences, or regulatory domains of different sizes and numbers not previously known. Parasitic or symbiotic bacteria tend not to have K(+) channels, while those showing lifestyle versatility often have more than one K(+)-channel gene. It is speculated that prokaryotic K(+) channels function to allow adaptation to environmental and metabolic changes, although the actual roles of these channels in prokaryotes are not yet known. Unlike enzymes in basic metabolism, K(+) channel, though evolved early, appear to play more diverse roles than revealed by animal research. Finding and sorting out these roles will be the goal and challenge of the near future.

Cloning and functional characterization of a superfamily of microbial inwardly rectifying potassium channels

“…Traditional methods for analyzing prokaryotic ion channels rely on recombinant expression in E. coli, affinity purification, and reconstitution into either lipid bilayers for electrophysiological analysis or into liposomes for macroscopic ion flux studies (10,11,13,14). A recent study (7) also reported successful expression of KcsA in mammalian cells using a codon-optimized synthetic gene.…”

“…Many of the recent advances in our understanding of K ϩ channel structure and function have been achieved through the study of prokaryotic homologs (11,13,14). But although many of these prokaryotic K ϩ channels share extensive homology with mammalian channels in the "transmembrane pore" region, their homology outside of this region is less well defined, e.g., the KcsA K ϩ channel from Streptomyces lividans, which has proven so useful in determining the mechanism of K ϩ permeation and channel gating, has no obvious mammalian counterpart.…”

Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain

“…R egulator of K þ conductance (RCK) domains control the activity of a variety of K þ channels and transporters, including the prokaryotic TrkA/H K þ transport complex and the eukaryotic large-conductance calcium-activated (BK) channel, through binding of cytoplasmic ligands such as ATP, H þ and Ca 2 þ (refs [1][2][3][4][5][6][7][8]. Thus, RCK domains transduce ligand binding to gate transmembrane K þ flux in response to signalling events and cellular metabolism, in organisms ranging from bacteria to humans.…”

Structure and function of multiple Ca 2+ -binding sites in a K + channel regulator of K + conductance (RCK) domain

“…calcium | lipid bilayer | cooperativity R egulator of K þ conductance (RCK) domains are structurally conserved ligand-binding domains that control the activity of a diverse array of K þ channels and transporters (1)(2)(3). Many prokaryotic RCK domains contain a conserved sequence motif for binding of nucleotides (NAD þ or ATP) (4,5).…”