Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biochemists Identify Protease Substrates Important to Bacterial Growth

28.06.2013
Reporting this month in Molecular Microbiology, Peter Chien and colleagues at the University of Massachusetts Amherst describe using a combination of biochemistry and mass spectrometry to “trap” scores of new candidate substrates of the protease ClpXP to reveal how protein degradation is critical to cell cycle progression and bacterial development. The new understanding could lead to identifying new antibiotic targets.

As Chien (pronounced Chen) explains, to carry out fundamental life processes such as growing and dividing, cells must orchestrate, in time and location, the production and degradation of hundreds of protein substrates. Even in simple bacteria, protein degradation is critical for making sure these organisms can grow and respond to their environment properly.


Peter Chien

Caulobacter crescentus (above) generates radically different cell types upon division. The ClpXP protease (illustrated below) recognizes and destroys many protein substrates that allow Caulobacter to differentiate into these different cell types. New work identifying scores of new candidate substrates of ClpXP to reveal how protein degradation is critical to cell cycle progression and bacterial development could lead to new antibiotic targets.

Scientists have known that a group of protein machines called energy-dependent proteases are responsible for the majority of this degradation, but what targets these machines recognize and how they do it has been unknown in many cases.

With the new series of experiments in the model bacteria Caulobacter crescentus in the Chien biochemistry and molecular biology laboratory, much more is now understood, he says. “We first generated a protease mutant that could recognize but not destroy its targets, acting as a ‘trap’ for protease substrates. After purifying this trap from living cells, we used mass spectrometry to identify proteins that were caught, finding over a hundred new candidate substrates. These targets covered all aspects of bacterial growth, including DNA replication, transcription and cytoskeletal changes.”

Next, they focused on one of these new targets in detail, a protein called TacA. Caulobacter grow by making two different cell types every time they divide. TacA is responsible for making sure that one of these cell types forms properly.

“We used biochemistry and highly purified proteins to identify what parts of TacA were important for degradation by the ClpXP protease,” Chien says. “We then made mutants of TacA that could not be degraded and found that when we expressed them in bacteria, these cells failed to properly develop into the correct cell types. Because developmental changes are essential for pathogenic bacteria to invade their host, these insights could potentially identify new antibiotic targets.”

The work was funded by a grant from the National Institute of General Medical Sciences at the National Institutes of Health and by UMass Amherst.

Peter Chien | Newswise
Further information:
http://www.umass.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>