Featured System - April 2011
Short description: Cells are filled with a salty soup of metal ions.
Cells are filled with a salty soup of metal ions. These ions are used in many different roles. Highly charged ions like iron and magnesium are often used as chemical tools by metalloenzymes, which capture individual metal ions and use them to recognize their substrates or catalyze their reactions. Sodium and potassium ions, on the other hand, are often used en masse for jobs like signaling or tuning the internal pressure of a cell. These jobs rely more on the overall concentration of the ions rather than a specific location of each one.
To control the concentration of ions, cells have evolved a complex collection of transporters and channels that control a constant traffic of ions across cell membranes. Some of these proteins, such as bacterial porins, are simple holes through the membrane, allowing anything smaller than a given size to pass. Others, however, are highly specific, selecting and transporting only one particular type of ion. Researchers at NYCOMPS have solved the structure of a new transporter for potassium ions, and discovered the atomic basis for its selectivity.
It is particularly challenging to build a channel that is specific for potassium, that doesn't also allow sodium to pass. Sodium and potassium both have a similar charge, so this doesn't provide a way to discriminate between the two. In addition, sodium ions are smaller than potassium, so you can't simply create a pore that measures the size. Previous structures of potassium channels have shown that cells use a trickier method to choose potassium ions by mimicking the way potassium ions interact with water.
Potassium channels contain a "selectivity filter" with a very specific arrangement of oxygen atoms, as shown in the Jmol image below. These oxygen atoms perfectly mimic the shell of waters that normally surround the ion when it is free in solution. The water shells are quite different between sodium and potassium ions, so by making the arrangement in the pore similar to the potassium hydration shell, the protein can favor the desolvation and passage of potassium rather than sodium. By taking advantage of this difference, some potassium channels allow only a single sodium ion to pass for every 10,000 potassium ions that flow through.
The TrkH structure, available in PDB entry 3pjz, adds several new wrinkles to the story of potassium transport. The previously studied channels are composed of four identical subunits that together form a symmetrical pore, with each subunit providing one fourth of the selectivity filter. The sequence of this filter is also highly constrained and the slightest mutation will abolish the selectivity. The channel in TrkH, on the other hand, is formed by a single protein chain. This chain forms all of the familiar functional structures needed for potassium passage, including a cage of oxygen atoms to act as the selectivity filter, and a set of pore helices angled to point their negative ends towards the potassium site. Surprisingly, the sequence of amino acids has several changes from the symmetrical channel proteins, showing that there are alternative ways to achieve specificity for potassium. However, although TrkH is known to select potassium ions over smaller ones like sodium and lithium, researchers are still testing whether it is as selective as the symmetrical potassium channels.
In cells, TrkH forms a dimer, with two side-by-side pores, and works along with several other proteins to transport potassium across the cell membrane. The structure of TrkH suggests its role as a potassium-specific channel, although biochemical studies have shown that the rate of passage is significantly slower than in other potassium channels. This may be due to a small loop that partially blocks the pore. It is still a mystery, however, whether TrkH is the engine that performs potassium transport, or simply works as part of a larger machine, acting as the filter that sorts potassium ions from other ions.
The ribose sugar bound to ribofuranosyl binding protein adopts a furanose conformation, forming a five-membered ring. You can compare this to a related structure of ribose with ribose binding protein, where the sugar adopts a six-membered pyranose ring, which is the typical conformation found in periplasmic sugar binding proteins. Both proteins form many hydrogen bonds (shown with thin bonds) to the sugar hydroxyl groups. However, ribose binding protein has three aromatic side chains (shown in
Cao, Y. et al. Crystal structure of a potassium ion transporter, TrkH. Nature doi:10.1038/nature09731.
Doyle, D. A. et al. The structure of the potassium channel: molecular basis of K+ conduction and specificity. Science 280, 69-77 (1998).