Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scissor-Like Enzyme That Trims Fatty Acids From Protein Molecules Points Toward Treatment of Infectious Disease

08.04.2013
UT Southwestern Medical Center researchers report that a pathogen annually blamed for an estimated 90 million cases of food-borne illness defeats a host’s immune response by using a fat-snipping enzyme to cut off cellular communication.

“Our findings provide insight into severe bacterial infectious diseases, as well as some forms of cancer, in which the attachment of fat molecules to proteins is an essential feature of the disease process,” said Dr. Neal Alto, assistant professor of microbiology and senior author of the study in today’s print edition of Nature. The study’s first author is Nikolay Burnaevskiy, a graduate student in microbiology.

The research group discovered a scissor-like enzyme that specifically cuts off functionally-essential fatty acids from proteins. “The one we studied in particular – a 14-carbon saturated fatty acid called myristic acid– has received a lot of attention due to its crucial role in the transformation of normal cells to cancer cells and for promoting cancer cell growth,” Dr. Alto said.

Because of the fat’s importance in human disease, researchers have tried for years to identify effective methods to remove them from proteins. “To our amazement, bacteria have invented the precise tool for the job,” Dr Alto said.

The bacteria used in this study, Shigella flexneri, are able to cross the intestinal wall and infect immune cells. Other intestinal bacteria, such as E. coli, are unable to do this. Once Shigella encounters immune system cells, including white blood cells such as macrophages, the bacteria use a needle-like complex to inject the cells with about 20 bacterial toxins.

The UTSW researchers conducted a series of experiments to characterize one of those toxins, called IpaJ, chosen in part because so little was known about the protein. They not only discovered IpaJ’s fat-cutting ability, but also determined how the protein disables the immune system’s communication infrastructure, which Dr. Alto compared to knocking out a bridge needed to deliver a package.

“Normally, a macrophage will engulf an invading bacteria and send out cytokines, proteins that act as cellular alert signals, which in turn recruit more immune cells to the site of infection,” Dr. Alto said. “When the macrophages engulf Shigella, however, the bacteria use IpaJ to cut fatty acids from proteins, which need those fats attached in order to sound the alarm. Doing so buys more time for the bacteria to grow and survive.

“It’s very interesting from a disease process point of view, but it’s also important because we now have a potential drug target,” said Dr. Alto. The next step, he said, will be to identify small molecule inhibitors that are specific to this fat-snipping protease and that might be developed into drugs.

The study in Nature received support from the National Institutes of Health, the Welch Foundation, and the Burroughs Wellcome Fund.

Other researchers from UTSW involved are Dr. Steven Patrie, assistant professor of pathology; former pediatrics fellow Dr. Thomas Fox, now an assistant professor of clinical pediatrics at Indiana University; Daniel Plymire, a graduate student of pathology in the molecular biophysics program; and graduate students Andrey Selyunin and Bethany Weigele, both in the molecular microbiology program. Researchers from the University of Cincinnati also participated in the investigation.

About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 100,000 hospitalized patients and oversee more than 2.1 million outpatient visits a year.
This news release is available on our World Wide Web home page at
www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via email,
subscribe at www.utsouthwestern.edu/receivenews

Deborah Wormser | Newswise
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>