Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cholesterol transporter structure decoded

21.03.2014

The three-dimensional structure of the transport protein TSPO opens up novel paths for the diagnosis and treatment of brain diseases

Joint press release of the DZNE and Max Planck Institute for Biophysical Chemistry


The cholesterol transporter TSPO in the outer mitochondrial membrane serves as a docking site for important diagnostic markers and for a number of drugs such as diazepam. Source: Łukasz Jaremko, Mariusz Jaremko, Markus Zweckstetter / DZNE, Max Planck Institute for Biophysical Chemistry and UMG

The word "cholesterol" is directly linked in most people's minds with high-fat foods, worrying blood test results, and cardiovascular diseases. However, despite its bad reputation, cholesterol is essential to our wellbeing:

It stabilizes cell membranes and is a raw material for the production of different hormones in the cell’s power plants – the mitochondria. Now, for the first time, scientists in Göttingen have solved the high-resolution structure of the molecular transporter TSPO, which introduces cholesterol into mitochondria.

This protein also serves as a docking site for diagnostic markers and different drugs, such as Valium. The detailed knowledge of its three-dimensional shape and function opens up new diagnostic and therapeutic perspectives.

Not only are mitochondria the most important energy supplier in living cells. They also produce steroid hormones such as testosterone and oestradiol, which control many processes in the body. The raw material for the production of steroid hormones is cholesterol, which must first be transported into mitochondria across two membranes.

This difficult task is carried out by a molecular transport protein named TSPO in the outer mitochondrial membrane. Using nuclear magnetic resonance spectroscopy, two teams working with the Göttingen-based scientists Markus Zweckstetter and Stefan Becker have now shown the complex three-dimensional structure of the protein “at work” in atomic detail.

The researchers achieved this methodical breakthrough by applying an ingenious trick: In their experiments, they coupled the transporter to an important diagnostic marker called PK11195; it was this complex that first gave the scientists analyzable results. In fact, the TSPO structure delivers more than just clues about how cholesterol is transported into the mitochondria.

"We now also have a much better understanding of how TSPO recognizes and binds to diagnostic markers and drugs", explains Markus Zweckstetter, head of research groups at the German Center for Neurodegenerative Diseases (DZNE), at the Max Planck Institute for Biophysical Chemistry, and at the Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) at the University Medical Center of Göttingen (UMG).

TSPO has long been successfully used in diagnostics and treatment of a number of diseases. "When the brain is injured or inflamed, its cells produce more TSPO. This fact is used in the diagnosis of neurodegenerative diseases such as Parkinson's and Alzheimer's", explains Stefan Becker, a protein chemist and Max Planck researcher who works next door to Zweckstetter.

Physicians also use radioactively tagged molecules such as PK11195 to visualize inflamed areas of the brain. A detailed understanding of how TSPO binds to such markers opens up novel paths for diagnostic imaging and could constitute an important step along the way to early detection of such diseases and inflammations.

TSPO also binds several medicinal drugs such as diazepam, also known by the trade name of Valium. Not only is diazepam a widely prescribed sedative; it is also used in the treatment of anxiety and epileptic seizures. The Göttingen researchers hope that detailed information about the transporter’s structure will help to develop new TSPO-binding drugs.

Original publication
Łukasz Jaremko, Mariusz Jaremko, Karin Giller, Stefan Becker, Markus Zweckstetter. Structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science 21 March 2014: Vol. 343 no. 6177 pp. 1363-1366 DOI: 10.1126/science.1248725

Contact
Prof. Dr. Markus Zweckstetter
Research Group Structural Biology in Dementia
German Center for Neurodegenerative Diseases (DZNE)
Research Group Structure Determination of Proteins Using NMR
Max Planck Institute for Biophysical Chemistry
University Medical Center Göttingen
+49 551 201-2220
markus.zweckstetter(at)dzne.de

Dr. Stefan Becker
Project Group Molecular Biology
Department of NMR-based Structural Biology
Max Planck Institute for Biophysical Chemistry
+49 551 201-2222
sabe(at)nmr.mpibpc.mpg.de

Dr. Carmen Rotte
Press and Public Relations
Max Planck Institute for Biophysical Chemistry
+49 551 201-1304
crotte(at)gwdg.de

Dr. Marcus Neitzert
Press and Public Relations
German Center for Neurodegenerative Diseases (DZNE)
+49 43302-271
marcus.neitzert(at)dzne.de

www.dzne.de

Markus Zweckstetter | EurekAlert!

Further reports about: Biology Biophysical DZNE Molecular Valium cholesterol diseases drugs mitochondrial protein

More articles from Life Sciences:

nachricht HKUST researchers discover ways to regenerate corticospinal tract axons
06.07.2015 | Hong Kong University of Science and Technology

nachricht Southampton researchers go with the flow to help protect endangered European eel
06.07.2015 | University of Southampton

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Viaducts with wind turbines, the new renewable energy source

Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.

The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions

A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Aluminum Clusters Shut Down Molecular Fuel Factory

06.07.2015 | Power and Electrical Engineering

Veja Mate Offshore orders 67 wind turbines including record long-term service

06.07.2015 | Press release

The quantum middle man

06.07.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>