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:6/9/2016)... 2016 Paris Police Prefecture ... security solution to ensure the safety of people and operations ... the major tournament Teleste, an international technology group ... announced today that its video security solution will be utilised ... up public safety across the country. The system roll-out is ...
(Date:6/3/2016)... 3, 2016 Das ... Nepal hat ein 44 ... geprägter Kennzeichen, einschließlich Personalisierung, Registrierung und IT-Infrastruktur, ... Produktion und Implementierung von Identitätsmanagementlösungen. Zahlreiche renommierte ... Januar teilgenommen, aber Decatur wurde als konformste ...
(Date:6/2/2016)... 2, 2016   The Weather Company , an IBM ... an industry-first capability in which consumers will be able to ... ask questions via voice or text and receive relevant information ... Marketers have long sought an advertising solution that ... be personal, relevant and valuable; and can scale across millions ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... -- Liquid Biotech USA , Inc. ... Research Agreement with The University of Pennsylvania ("PENN") ... patients.  The funding will be used to assess ... outcomes in cancer patients undergoing a variety of ... to support the design of a therapeutic, decision-making ...
(Date:6/24/2016)... ... , ... While the majority of commercial spectrophotometers and fluorometers use the z-dimension ... are higher end machines that use the more unconventional z-dimension of 20mm. Z-dimension ... bottom of the cuvette holder. , FireflySci has developed several Agilent flow cell ...
(Date:6/23/2016)... , June 23, 2016   Boston ... of novel compounds designed to target cancer stemness ... has been granted Orphan Drug Designation from the ... treatment of gastric cancer, including gastroesophageal junction (GEJ) ... inhibitor designed to inhibit cancer stemness pathways by ...
(Date:6/23/2016)... Lawrence, MA (PRWEB) , ... June 23, 2016 ... ... the Peel Plate® YM (Yeast and Mold) microbial test has received AOAC Research ... test platform of microbial tests introduced last year,” stated Bob Salter, Vice President ...
Breaking Biology Technology: