Using highly sensitive fluorescent probes, a team of scientists from the University of Connecticut has captured the never-before-seen structural dynamics of an important protein channel inside the cell's primary power plant – the mitochondrion.
The UConn team's study found that the channel complex - known as the translocase of the inner mitochondrial membrane 23 or TIM23 – is not only directly coupled to the energized state of the mitochondrial inner membrane as scientists have long suspected, it also changes its fundamental structure - altering the helical shape of protein segments that line the channel - when voltage along the membrane's electrical field drops.
The research, which appears this week in the peer-reviewed journal Nature Structural & Molecular Biology, explains how the energized state of the membrane drives the structural dynamics of membrane proteins and sheds new light on how cellular transport systems harness energy to perform their work inside the cell.
It also shows how fluorescent mapping at the subcelllar level may reveal new insights into the underlying causes of neurodegenerative and metabolic disorders associated with mitochondrial function.
In an overview of the research accompanying the paper's publication, Nikolaus Pfanner of the University of Freiberg in Germany and an international leader in the field of cellular protein trafficking, and several members of his research group, called the study "a major step towards a molecular understanding of a voltage-gated protein translocase."
"The molecular nature of voltage sensors in membrane proteins is a central question in biochemical research," Pfanner and his colleagues said. "The study…is not only of fundamental importance for our understanding of mitochondrial biogenesis, but also opens up new perspectives in the search for voltage-responsive elements in membrane proteins."
To conduct the study, UConn researchers incorporated cysteine residues modified with a fluorescent probe at specific positions along a transmembrane segment of a TIM23 complex derived from a common species of yeast, Saccharomyces cerevisiae. The team then monitored the probes in real time to observe how the channel's voltage-gating and structure responded to induced changes in the inner membrane's electrical field.
"It's an indirect way of looking at the structure of something, but because we are able to look into an actually functioning mitochondrion, it's given us a whole world of new information," says Nathan N. Alder, an assistant professor in the Department of Molecular and Cell Biology in UConn's College of Liberal Arts and Sciences and the research team's leader.
The study was supported by grants from the National Science Foundation, the National Institutes of Health and the Robert A. Welch Foundation.
"That the magnitude of the voltage gradient across the membrane could play a significant role in defining the structure of these proteins is probably one of the most significant elements of this research," Alder says.
The next phase of the research will look toward isolating the TIM23 protein channel complex in an artificial system to see if it continues to respond to voltage fluctuations outside of its natural habitat. The research team is also hoping to identify the particular parts of the protein complex that are acting as voltage sensors.
"Once we start to identify exactly what is the voltage sensor, we will have a better understanding of the translocase process and ultimately we can apply this knowledge to other kinds of protein transporters whose dysfunction has been implicated in the etiology of diseases such as cardiovascular disease and cancer," Alder says. "If their function is tied to the energized state of the membrane, we'll be able to see whether defects in that ability to couple to the membrane might be associated with the pathogenesis of these diseases."
Colin Poitras | EurekAlert!
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
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
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology