Navigation Links
Key difference in how TB bacteria degrade doomed proteins
Date:10/17/2010

UPTON, NY Scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory and Stony Brook University have discovered a key difference in the way human cells and Mycobacterium tuberculosis bacteria, which cause TB, deliver unwanted proteins marked with a "kiss of death" sequence to their respective cellular recycling factories. This critical difference, described in a paper published online October 17, 2010, in the journal Nature Structural and Molecular Biology, may help scientists design drugs to disable the bacterial system while leaving normal human protein recycling centers intact.

"With tuberculosis infecting a third of the world's population, primarily in developing countries, there is great need for new, effective TB treatments," said study co-author Huilin Li, a Brookhaven biophysicist and associate professor at SBU. "Our research seeks to understand the protein-recycling mechanism of TB bacteria, because it is one of the microbe's keys to survival in human cells.* Targeting this system with small-molecule-based drugs could inhibit the bacteria and effectively treat TB."

The catch is that human cells have a similar protein-recycling system, essential for their survival, which could also be destroyed by inhibitory drugs. "It's important to find differences between the species so we can target features unique to the bacterial system," Li said.

Li has previously looked at differences in the cellular structure known as a proteasome that chops up the unwanted proteins [see links below]. The current study examined the way proteins destined for degradation are recognized by the bacterial proteasome before entering that structure.

Using beams of high-intensity x-rays at the Lab's ["http://www.nsls.bnl.gov/">National Synchrotron Light Source (NSLS), the scientists determined atomic-level structures of the portion of the bacterial proteasome that identifies the unwanted protein's "kiss of death" marker sequence as well as structures of the marker sequence as it binds with the proteasome.

Based on the structures, the scientists describe a detailed mechanism by which coiled, tentacle-like arms protruding from the proteasome identify the death sentence label, causing a series of protein-folding maneuvers that pull the doomed protein into the degradation chamber.

Importantly, this interaction between the bacterial proteasome and the marker sequence is unique to bacteria. Human cells use a different marker protein and a completely different mechanism for drawing doomed proteins into the proteasome. Thus the details of proteasome-substrate interaction revealed by the current study may provide highly specific targets for the development of new anti-tuberculosis therapies.


'/>"/>

Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
Source:Eurekalert

Related biology news :

1. Researchers note differences between people and animals on calorie restriction
2. Study sheds light on genetic differences that cause a childhood eye disease
3. Study identifies genetic variants giving rise to differences in metabolism
4. Genetic differences between yeasts greater than those between humans and chimpanzees
5. Red wine vs. white? It makes no difference when it comes to breast-cancer risk
6. Differences in neighborhood food environment may contribute to disparities in obesity
7. The host makes all the difference
8. Difference in fat storage may explain lower rate of liver disease in African-Americans
9. Gene linked to lupus might explain gender difference in disease risk
10. Differences among exercisers and nonexercisers during pregnancy
11. Differences among exercisers and nonexercisers during pregnancy
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/3/2017)... , April 3, 2017  Data ... precision engineering platform, detected a statistically significant ... product prior to treatment and objective response ... the potential to predict whether cancer patients ... to treatment, as well as to improve ...
(Date:3/29/2017)...  higi, the health IT company that operates the ... , today announced a Series B investment from ... The new investment and acquisition accelerates higi,s strategy to ... population health activities through the collection and workflow integration ... collects and secures data today on behalf of over ...
(Date:3/24/2017)... 2017 Research and Markets has announced the ... & Trends - Industry Forecast to 2025" report to their ... The Global ... CAGR of around 15.1% over the next decade to reach approximately ... the market estimates and forecasts for all the given segments on ...
Breaking Biology News(10 mins):
(Date:4/19/2017)... , April 19, 2017 A new report published by ... Forecast, 2014-2022 ," the global market was valued at $6,769 million in 2015, ... 9.6% from 2016 to 2022. ... Allied Market Research Logo ...      (Logo: http://photos.prnewswire.com/prnh/20140911/647229) The ...
(Date:4/19/2017)... SOUTH SAN FRANCISCO, Calif. , April 19, ... VCYT ) today announced that it ... after close of market on Wednesday, May 3, 2017. ... call and webcast at 4:30 p.m. Eastern Time to discuss ... The live webcast and subsequent replay may ...
(Date:4/18/2017)... ... April 18, 2017 , ... ... awarded Channel Partners 2017 Next-Gen Solution Provider. , Channel Partners program recognizes IT ... with their vision, innovation, and advocacy of the channel during transition and convergence. ...
(Date:4/18/2017)... , ... April 18, 2017 , ... ... that Dr. Mark Boguski has been appointed to the role of Chief Medical ... medicine solutions. , “Dr. Boguski is widely considered a visionary leader in ...
Breaking Biology Technology: