Featured Research

from universities, journals, and other organizations

Mechanism to repair clumped proteins explained

Date:
November 21, 2012
Source:
Heidelberg, Universität
Summary:
Clumped proteins can be dissolved with the aid of cellular repair systems -- a process of critical importance for cell survival especially under conditions of stress. Researchers have now decrypted the fundamental mechanism for dissolving protein aggregates that involves specific molecular chaperones.

Clumped proteins can be dissolved with the aid of cellular repair systems -- a process of critical importance for cell survival especially under conditions of stress. Heidelberg researchers have now decrypted the fundamental mechanism for dissolving protein aggregates that involves specific molecular chaperones. Scientists from the Center for Molecular Biology of Heidelberg University and the German Cancer Research Center cooperated with experts from the Heidelberg Institute for Theoretical Studies on the project.

Related Articles


The results of the research appeared in two simultaneously published articles in Nature Structural & Molecular Biology.

Proteins consist of long chains of successive amino acids and perform vital functions in every cell. To function, every amino acid chain must first assume a specific three-dimensional structure -- it has to fold itself. A change in growth conditions, such as an increase in ambient temperature, can cause proteins to lose their structure and unfold. Unfolded protein chains run the risk of clumping, forming protein aggregates. "If such aggregates form, the proteins cannot function, which can lead to cell death, which we see in neurodegenerative diseases such as Alzheimer's and Parkinson's, and even in ageing processes," explains Prof. Dr. Bernd Bukau, Director of the Center for Molecular Biology of Heidelberg University (ZMBH), who is also a researcher at the German Cancer Research Center (DKFZ).

But clumping does not necessarily mean the end of a protein's life cycle. "Cells have repair systems for damaged proteins, so-called molecular chaperones, that can dissolve even aggregated proteins and refold them," clarifies Dr. Axel Mogk, also a member of the ZMBH and DKFZ. The repair is carried out by a cooperating team of two chaperones, called Hsp70 and Hsp100. The Heidelberg researchers were able to demonstrate that the activity of the Hsp100 chaperone is regulated by a built-in molecular switch.

This switch is first positioned to curtail energy consumption, i.e. ATP hydrolysis, and thereby the activity of the Hsp100 chaperone. The cooperating Hsp70 protein changes the position of the switch and activates Hsp100 directly at the protein aggregate. In this state, the "motor" of the ring-shaped Hsp100 protein runs at full speed, reaches top performance and is able to extract individual chains from the aggregate. Afterwards, the extracted, unfolded protein can start the folding process over. The results of the Heidelberg research also show that the built-in switch's control of Hsp100 activity is of vital importance for this complicated protein machine, because the loss of regulation in hyperactive, i.e. permanently activated, Hsp100 protein variants leads to cell death.

The research collaboration falls under the DKFZ-ZMBH Alliance, the strategic cooperation of the German Cancer Research Center and the Center for Molecular Biology of Heidelberg University. The Heidelberg Institute for Theoretical Studies (HITS) develops new theoretical approaches to interpreting the burgeoning amount of experimental data.


Story Source:

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


Journal References:

  1. Fabian Seyffer, Eva Kummer, Yuki Oguchi, Juliane Winkler, Mohit Kumar, Regina Zahn, Victor Sourjik, Bernd Bukau, Axel Mogk. Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA disaggregase at aggregate surfaces. Nature Structural & Molecular Biology, 2012; DOI: 10.1038/nsmb.2442
  2. Yuki Oguchi, Eva Kummer, Fabian Seyffer, Mykhaylo Berynskyy, Benjamin Anstett, Regina Zahn, Rebecca C Wade, Axel Mogk, Bernd Bukau. A tightly regulated molecular toggle controls AAA disaggregase. Nature Structural & Molecular Biology, 2012; DOI: 10.1038/nsmb.2441

Cite This Page:

Heidelberg, Universität. "Mechanism to repair clumped proteins explained." ScienceDaily. ScienceDaily, 21 November 2012. <www.sciencedaily.com/releases/2012/11/121121104416.htm>.
Heidelberg, Universität. (2012, November 21). Mechanism to repair clumped proteins explained. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2012/11/121121104416.htm
Heidelberg, Universität. "Mechanism to repair clumped proteins explained." ScienceDaily. www.sciencedaily.com/releases/2012/11/121121104416.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. 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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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