Featured Research

from universities, journals, and other organizations

Exploring New Therapy Strategies For Tuberculosis

Date:
June 22, 2009
Source:
ETH Zurich
Summary:
Certain protein degradation complexes, molecular "shredders" dispose of protein garbage. Molecular machines of this kind have now been successfully decoded and show how proteins in tuberculosis bacteria are prepared for disposal.

The figure shows how proteins are prepared for their degradation in a tuberculosis bacterium.
Credit: Wolfgang Kress & Frank Striebel / ETH Zurich

Certain protein degradation complexes, molecular “shredders”, dispose protein garbage. Molecular machines of that kind belong to the area of expertise of Eilika Weber-Ban, who together with her team has now successfully decoded how proteins in tuberculosis bacteria are prepared for disposal.

The fact that bacteria also possess a special “small” protein that can be attached to other proteins to alter their fate became known only recently. The “small” protein, which has been named “Pup”, helps to dispose of other proteins. However, its attachment may also control and regulate other important processes in the cells. “Pup” acts as a kind of marker. By being attached to another protein, it signals to the degradation complex that the marked protein is ready for disposal.

Mode of operation investigated in the test tube

Eilika Weber-Ban, research group leader at the Institute of Molecular Biology & Biophysics of ETH Zurich, and her team have now succeeded in understanding how the “Pup” protein works in the tuberculosis pathogen Mycobacterium tuberculosis. In the test tube, the researchers were able to show how Pup is attached to proteins. By doing so, the scientists discovered a new enzyme which they call “Dop”. The results were published recently in Nature Structural & Molecular Biology. The study may provide the basis for therapeutic strategies for people suffering from tuberculosis, especially in the case of patients in whom the pathogen has acquired resistance to antibiotics.

Coupling in two steps

The “Pup” degradation signal is coupled to a protein in two steps: first, “Dop” modifies the degradation signal to allow another enzyme to couple the modified “Pup” to its target protein. Now, the “molecular shredders” come into play: due to the attached Pup-signal the protein is ready to enter the “shredders”. These consist of a protein complex, which can be divided into two parts according to their function. Weber-Ban describes the entrance region, where the marked proteins enter through pores into the protease complex, as the engine. “Its task is to unroll the folded protein, which can be thought of as a ball of yarn, so it can be threaded into the second part of the shredder and chopped into pieces”, Weber-Ban explains. This function is carried out by molecular “scissors” inside the shredder.

In the eighties, scientists discovered a similar marker protein that disposes proteins in cells of multi-cellular organisms such as plants, animals and humans. The scientists were awarded the 2004 Nobel Prize for Chemistry for their discovery. However, until late 2008 it was unknown that proteins of that kind also existed in bacteria. According to the ETH researchers, however, the bacterial and human marker proteins differ markedly in their structure and in the way they function although they both ensure the degradation of proteins in cells.

No side-effects

It is still unclear which molecular processes are affected by “Pup”-mediated degradation in the tuberculosis pathogen. However, it is known that bacteria without this complex degradation mechanism cannot survive in the epithelial cells of the lungs. “This is why both the marker proteins and the degradation complex are suitable targets for therapy strategies”, says Weber-Ban. She points out that the marking system is a particularly good target in this respect, as it differs from that of humans and therefore drugs targeting the bacterial Pup-system should have no side-effects for humans.


Story Source:

The above story is based on materials provided by ETH Zurich. Note: Materials may be edited for content and length.


Journal Reference:

  1. Striebel et al. Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes. Nature Structural & Molecular Biology, 2009; 16 (6): 647 DOI: 10.1038/nsmb.1597

Cite This Page:

ETH Zurich. "Exploring New Therapy Strategies For Tuberculosis." ScienceDaily. ScienceDaily, 22 June 2009. <www.sciencedaily.com/releases/2009/06/090613105602.htm>.
ETH Zurich. (2009, June 22). Exploring New Therapy Strategies For Tuberculosis. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2009/06/090613105602.htm
ETH Zurich. "Exploring New Therapy Strategies For Tuberculosis." ScienceDaily. www.sciencedaily.com/releases/2009/06/090613105602.htm (accessed August 22, 2014).

Share This




More Plants & Animals News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Farm Resurgence Grows With Younger Crowd

Farm Resurgence Grows With Younger Crowd

AP (Aug. 22, 2014) New England farms are seeing a surge in younger farm hands as the 'buy local' food movement grows across the country. (Aug. 22) Video provided by AP
Powered by NewsLook.com
Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Terrifying City-Dwelling Spiders Are Bigger And More Fertile

Terrifying City-Dwelling Spiders Are Bigger And More Fertile

Newsy (Aug. 21, 2014) According to a new study, spiders that live in cities are bigger, fatter and multiply faster. Video provided by Newsy
Powered by NewsLook.com
Did Russia Really Find Plankton On The ISS? NASA Not So Sure

Did Russia Really Find Plankton On The ISS? NASA Not So Sure

Newsy (Aug. 21, 2014) Russian cosmonauts say they've found evidence of sea plankton on the International Space Station's windows. NASA is a little more skeptical. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins