Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hot on the trail of metabolic diseases and resistance to antibiotics

28.03.2012
Proteins belonging to the large and important family of ABC transporters have been associated with metabolic diseases and can cause resistance to antibiotics.
Biochemists from the University of Zurich and the NCCR Structural Biology have succeeded in determining the atomic structure of a new ABC transporter. The insights gained could give rise to new therapies to treat multi-resistant bacteria, cystic fibrosis or gout, for instance.

ABC transporters are membrane proteins that actively pump a wealth of molecules across the membrane. Over 40 different ABC transporters perform vital functions in humans. Genetic defects in ABC transporters can trigger metabolic diseases such as gout, neonatal diabetes or cystic fibrosis, and certain ABC transporters also cause resistance to a wide range of drugs. In tumor cells, increased amounts of ABC transporters that pump chemotherapeutic substances out of the cell are often produced, thus rendering anticancer drugs ineffective. Analogous mechanisms play a key role in many pathogenic bacteria: ABC transporters carry antibiotics out of the cell – multi-resistant bacteria are the result.

Detailed side-view of the ABC transporter “TM287/288”. The transporter adopts is inward-facing state. The two different protein chains are marked in turquoise and pink. Picture: UZH


Transport mechanism: The inwardly open transporters can bind a molecule, such as an antibiotic (yellow star) – adopts its outward-facing state and releases the previously bound antibiotic. Picture:UZH

Despite their major importance in biology and medicine, so far the atomic structure of only a few ABC transporters has been decoded. Now, under the supervision of Markus Seeger and Professor Markus Grütter, PhD student Michael Hohl and senior scientist Christophe Briand have succeeded in cracking the atomic structure of the new ABC transporter “TM287/288”.

Illuminating asymmetry

The membrane protein originates from a thermophilic bacterium. Compared to structures already known, “TM287/288” has two different protein chains that assemble into a heterodimer. About half of the 40 human ABC transporters are heterodimers. “The asymmetries discovered enable us to consider the role of ABC transporters in a new light,” explains Seeger. “In the longer term, our results could help develop new medication against multi-resistant bacteria or tumors that are difficult to treat. They also make new approaches to curing or alleviating hereditary diseases possible,” concludes Grütter.

Literature:
Michael Hohl, Christophe Briand, Markus G. Grütter & Markus A. Seeger. Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation. In: Nature Structural & Molecular Biology, March 28, 2012. Doi: 10.1038/nsmb.2267

Contact:
Dr. Markus Seeger
Department of Biochemistry
University of Zurich
Tel.: +41 44 635 55 52
Email: m.seeger@bioc.uzh.ch

Nathalie Huber | Universität Zürich
Further information:
http://www.bioc.uzh.ch
http://www.structuralbiology.uzh.ch

More articles from Life Sciences:

nachricht Scientists spin artificial silk from whey protein
24.01.2017 | Deutsches Elektronen-Synchrotron DESY

nachricht Choreographing the microRNA-target dance
24.01.2017 | UT Southwestern Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists spin artificial silk from whey protein

X-ray study throws light on key process for production

A Swedish-German team of researchers has cleared up a key process for the artificial production of silk. With the help of the intense X-rays from DESY's...

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Breaking the optical bandwidth record of stable pulsed lasers

24.01.2017 | Physics and Astronomy

Choreographing the microRNA-target dance

24.01.2017 | Life Sciences

Spanish scientists create a 3-D bioprinter to print human skin

24.01.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>