New research at the University of Arkansas shows that arginine – one of 20 common amino acids – does not change its positive charge when inserted into the lipid environment of the cell membrane.
The discovery contributes to the understanding of cell membrane properties, and in the long term, could inform treatment of neurodegenerative diseases, said Roger Koeppe II, Distinguished Professor in the Department of Chemistry and Biochemistry at the U of A.
The study was published in the journal Biochemistry.
Jordana Thibado, a recent honors graduate of the U of A, was the study's lead author. Her discovery builds on work conducted by researchers in Koeppe's lab, who found that a similar amino acid, lysine, has a tendency to release its positive charge when inserted into lipids that represent the cell membrane environment.
"Forming a model to understand the physics of transmembrane proteins is extremely important for understanding physiology that we rely on every millisecond," Thibado said. "Down the line, this work could advance drug design for diseases like Alzheimer's and Parkinson's where protein aggregation can occur."
Thibado inserted arginine into models of two peptide helices that mimic protein components of the cell membrane, at different positions on the helix. Thibado then explored what happened when the helices were exposed to cholesterol.
"The future challenge is to figure out why cholesterol has such a big effect on one of these samples, and not on the other, because we don't understand why this is happening," Koeppe said. "Cholesterol is much studied, but many of the fundamental properties still are not well understood."
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Jordana K. Thibado et al. Influence of High pH and Cholesterol on Single Arginine-Containing Transmembrane Peptide Helices, Biochemistry (2016). DOI: 10.1021/acs.biochem.6b00896