The findings, reported in the Dec. 15 issue of Nature, are expected to be welcome news for chemists and biophysicists, both experimentalists and theoreticians, because they have previously relied on theoretical estimations to predict protonation states -- whether an amino acid is charged or not. Appropriate experimental benchmarks also had been lacking.
All cells have membrane proteins that form channels to allow water and/or ions to pass through. Malfunctions have been linked to such problems as hypertension, abnormal insulin secretion, abnormal heart conditions and brain seizures. As a result, these membrane proteins are often targeted by drug treatments.
Previous approaches didn't provide sufficient resolution to let researchers accurately detect the association and dissociation of protons to and from individual amino-acid residues in real time.
Using the patch-clamp technique, the researchers were able to probe the electrostatic properties of the inner lining of the ion-channel's pore, and, from there, they inferred the rotational angle of the pore-lining alpha-helices in the open state.
In this case, researchers focused on the muscle nicotinic acetylcholine receptor, a membrane protein that mediates voluntary muscle contraction.
"Our paper has implications that are specific to this receptor, but many of the findings can be extended to several other membrane proteins," said Claudio Grosman, a professor of molecular and integrative physiology at Illinois.
"We are working with the open state of the ion channel, and we now know how the helices that line the pore are oriented. This was not known before," Grosman sai
Source:University of Illinois at Urbana-Champaign