Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Peering into the protein pathways of a cell

UConn researchers shed new light on how cellular transport systems harness energy to perform their work inside the cell

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!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>