Featured Research

from universities, journals, and other organizations

How cells dispose of their waste: Researchers reveal the structure of the cellular protein degradation machinery

Date:
January 24, 2012
Source:
Max-Planck-Gesellschaft
Summary:
Defective proteins that are not disposed of by the body can cause diseases such as Alzheimer’s or Parkinson’s. Scientists recently succeeded in revealing the structure of the cellular protein degradation machinery (26S proteasome) by combining different methods of structural biology. The results represent an important step forward in the investigation of the 26S proteasome.

Reconstruction of the 26S proteasome: The “regulatory particle” (in blue) detects the proteins tagged with ubiquitin and prepares them for degradation. The “core particle” (in red) breaks the proteins down into their single components.
Credit: Image by Julio Ortiz / © MPI of Biochemistry

Max Planck researchers reveal the structure of the cellular protein degradation machinery. Defective proteins that are not disposed of by the body can cause diseases such as Alzheimer's or Parkinson's. Scientists at the Max Planck Institute (MPI) of Biochemistry recently succeeded in revealing the structure of the cellular protein degradation machinery (26S proteasome) by combining different methods of structural biology. The results of collaboration with colleagues from the University of California, San Francisco and the Swiss Federal Institute of Technology Zurich (ETH Zürich) represent an important step forward in the investigation of the 26S proteasome.

The findings have now been published in the Proceedings of the National Academy of Sciences.

At any given point in time, cells may contain only the proteins that are needed at exactly this moment. Otherwise, undesirable reactions can occur which could cause cancer or other diseases. Furthermore, the proteins have to be folded correctly to fulfill their tasks. Misfolded proteins can clump into aggregates, and neurodegenerative diseases such as Alzheimer's or Parkinson's may be the consequence. In order to prevent this, several mechanisms in the body regulate the number of proteins in the cell and degrade proteins if necessary.

"Cellular waste disposal" -- the 26S proteasome -- plays an important role in protein degradation. First, misfolded and potentially dangerous proteins are tagged with molecules called ubiquitin. The 26S proteasome detects the tagged proteins and breaks them down into small fragments, which are then recycled. Scientists in the team of Wolfgang Baumeister, head of the research department "Molecular Structural Biology" at the MPI of Biochemistry, have now been able to reveal its structure.

Many puzzle pieces lead to one structure

"The structure of the 26S proteasome changes continuously," explained Friedrich Förster, head of the research group "Modeling of Protein Complexes" at the MPI of Biochemistry. "That is why until now it could not be explained by means of traditional approaches, such as only using X-ray crystallography. We had to combine different methods to be successful." Electron microscopy and mass spectrometry helped to reveal the general structure of the 26S proteasome. X-ray crystallography provided detailed insights into specific areas of the molecule. The researchers then used computer software to integrate the different data and generate an overall picture.

Based on these results, the researchers next want to find out how the different mechanisms of protein degradation work in detail. "We have already developed a hypothesis of how exactly the 26S proteasome detects tagged proteins and processes them," said Stefan Bohn, scientist at the MPI of Biochemistry. The complete elucidation of the 26S proteasome and its underlying mechanisms could also be of medical importance: "Cellular waste disposal" is a therapeutic target for cancer und neurodegenerative diseases.


Story Source:

The above story is based on materials provided by Max-Planck-Gesellschaft. Note: Materials may be edited for content and length.


Journal References:

  1. Keren Lasker, Friedrich Förster, Stefan Bohn, Thomas Walzthoeni, Elizabeth Villa, Pia Unverdorben, Florian Beck, Ruedi Aebersold, Andrej Sali, Wolfgang Baumeister. Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1120559109
  2. G. R. Pathare, I. Nagy, S. Bohn, P. Unverdorben, A. Hubert, R. Korner, S. Nickell, K. Lasker, A. Sali, T. Tamura, T. Nishioka, F. Forster, W. Baumeister, A. Bracher. The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together. Proceedings of the National Academy of Sciences, 2011; 109 (1): 149 DOI: 10.1073/pnas.1117648108
  3. E. Sakata, S. Bohn, O. Mihalache, P. Kiss, F. Beck, I. Nagy, S. Nickell, K. Tanaka, Y. Saeki, F. Forster, W. Baumeister. Localization of the proteasomal ubiquitin receptors Rpn10 and Rpn13 by electron cryomicroscopy. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1119394109

Cite This Page:

Max-Planck-Gesellschaft. "How cells dispose of their waste: Researchers reveal the structure of the cellular protein degradation machinery." ScienceDaily. ScienceDaily, 24 January 2012. <www.sciencedaily.com/releases/2012/01/120123152045.htm>.
Max-Planck-Gesellschaft. (2012, January 24). How cells dispose of their waste: Researchers reveal the structure of the cellular protein degradation machinery. ScienceDaily. Retrieved April 19, 2014 from www.sciencedaily.com/releases/2012/01/120123152045.htm
Max-Planck-Gesellschaft. "How cells dispose of their waste: Researchers reveal the structure of the cellular protein degradation machinery." ScienceDaily. www.sciencedaily.com/releases/2012/01/120123152045.htm (accessed April 19, 2014).

Share This



More Plants & Animals News

Saturday, April 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Vermont Goat Meat Gives Refugees Taste of Home

Vermont Goat Meat Gives Refugees Taste of Home

AP (Apr. 18, 2014) — Dairy farmers and ethnic groups in Vermont are both benefiting from a unique collaborative effort that's feeding a growing need for fresh and affordable goat meat. (April 18) Video provided by AP
Powered by NewsLook.com
First Ever 'Female Penis' Discovered In Animal Kingdom

First Ever 'Female Penis' Discovered In Animal Kingdom

Newsy (Apr. 18, 2014) — Not only are these newly discovered bugs' sex organs reversed, but they also mate for up to 70 hours. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) — A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
The Great British Farmland Boom

The Great British Farmland Boom

Reuters - Business Video Online (Apr. 17, 2014) — Britain's troubled Co-operative Group is preparing to cash in on nearly 18,000 acres of farmland in one of the biggest UK land sales in decades. As Ivor Bennett reports, the market timing couldn't be better, with farmland prices soaring over 270 percent in the last 10 years. Video provided by Reuters
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