“Historically, lysine and arginine, both basic amino acids, were considered to have very similar properties and therefore to be essentially interchangeable,” said Denise Greathouse, a research associate professor in the department of chemistry and biochemistry. “Our results demonstrate that despite their similarities, the differences in their behavior in membrane environments provide important clues for understanding membrane protein function.”
The findings, which appear in the January issue of the journal Proceedings of the National Academy of Sciences, address long-standing questions in the study of protein structure and function and help explain how charged amino acids are able to modulate the behavior of proteins in cellular membranes.
Greathouse, former doctoral students Nicholas Gleason and Vitaly Vostrikov, and Roger Koeppe II, Distinguished Professor of chemistry and biochemistry, wrote the article, “Buried lysine, but not arginine, titrates and alters transmembrane helix tilt.”
Proteins do nearly all the work in the cells of our bodies, ranging from brain function and nerve transmission to metabolic energy production and muscular contraction. Moreover, many diseases are associated with defects in protein function. Future advances in the diagnosis and treatment of human disease will depend upon better understanding of the thousands of proteins that are encoded within the genomes of humans and human pathogens.
The structure and function of membrane proteins both play a crucial role in cell signaling and the regulation of biological function. The authors developed experimental methods that determine how lysine and arginine interact in the lipid bilayer membrane environment. In the last 10 years there have been computational predictions of the behavior of lysine and arginine in the membrane but not methods to test those predictions.
“It is the first measurement of its type, its complexity makes it an elegant method, and it opens the door for other people to apply these methods on biologically important problems,” Koeppe said. “There is a lot of interest in trying to understand what’s going on in these membranes, especially with protein molecules that carry particular electric charges. Unless we can understand it at the fundamental level, then we can’t extrapolate it to the nervous system. We’re trying to develop foundational knowledge that is needed to understand the nervous system.
“We’re excited about this study because it makes available knowledge that other researchers can use,” he said. “Those making the computer predictions can refine their methods and make better predictions because they know that they were able to reproduce some of our results.”
Lysine and arginine are ionizable, which means they can have a positive electric charge. The research team created a framework for experimentation that uses magnetic resonance imaging to measure whether the groups remain charged or become uncharged as the acidity or the pH of the environment is changed. To make their procedure work, the scientists synthesized peptides, which are chemical compounds consisting of several or more linked amino acids. To enable the magnetic resonance experiments, some of the hydrogen atoms in the peptides were replaced with deuterium, a heavy isotope of hydrogen.
“We’ve spent about 15 years doing this,” Koeppe said. “We developed first- and second-generation families of model peptides, and we examine them in model lipid membranes in order to understand the properties of real cell membranes and real cell proteins. This is at a molecular level. We are not even up to the cell yet.”
Vostrikov and Gleason earned their doctorates in 2011 and 2012, respectively. Vostrikov is a postdoctoral fellow at the University of Minnesota and Gleason teaches chemistry at Shiloh Christian School in Springdale.
The National Science Foundation provided the grant for the experiments described in the Proceedings of the National Academy of Sciences. The National Institutes of Health provided the financial support for the early stages of development of the peptide framework and for the facilities.
The research was performed in the U of A’s Center for Protein Structure and Function, which was established in 2000 in the J. William Fulbright College of Arts and Sciences to develop a detailed understanding of the structure and function of proteins that could lead to improved treatments of human disease. Center scientists study proteins involved in cancer, heart disease, osteoporosis, the flu and other diseases and conditions.
Contact:Roger Koeppe II, Distinguished Professor, chemistry and biochemistr
Roger Koeppe | Newswise
Funding of Collaborative Research Center developing nanomaterials for cancer immunotherapy extended
28.06.2017 | Johannes Gutenberg-Universität Mainz
Zeolite catalysts pave the road to decentral chemical processes Confined space increases reactivity
28.06.2017 | Technische Universität München
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
28.06.2017 | Power and Electrical Engineering
28.06.2017 | Life Sciences
28.06.2017 | Awards Funding