Grosman and Cymes use an approach called patch-clamp recording, a single-molecule technique that allows them to measure binding and unbinding of single protons in functioning molecules, something that other powerful approaches cannot achieve.
With patch-clamp recording, the researchers could see the charge state of working ion channels in living cells. They saw that, in anion-selective channels, the basic residues appear to have the expected positive charge. However, in the cation-selective channels, the lysine or arginine seems to be tucked into the protein structure so that it cannot accept a proton from the surrounding environment and instead remains neutral. This allows cation-selective channels to keep the basic residues in their sequential place without having to substitute them with other amino acids.
"These channels are the subject of a lot of computational studies. Before this paper, if researchers had to model these channels, they would always run the simulation with all the ionizable residues charged, and the simulation could well be wrong," Grosman said. "With small tweaks, changing the position of the amino acid changes its properties. For a lysine to be protonated or deprotonated is a big difference. It's not trivial."
"Overall, we want to emphasize the notion that the properties of these chargeable amino acids depends strongly on their particular microenvironment in the whole protein," Grosman added.
While the study focused on muscle acetylcholine receptors, Grosman believes the "tucked-in" principle holds t
|Contact: Liz Ahlberg|
University of Illinois at Urbana-Champaign