Mechanism to Repair Clumped Proteins Explained
News Nov 23, 2012
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. 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.
Graphene on Toast, Anyone?News
Scientists who introduced laser-induced graphene (LIG) have enhanced their technique to produce what may become a new class of edible electronics. The lab is investigating ways to write graphene patterns onto food and other materials to quickly embed conductive identification tags and sensors into the products themselves.READ MORE
Insulin Goes Viral: Diabetes and Cancer-causing Mechanisms ExploredNews
Every cell in your body responds to the hormone insulin, and if that process starts to fail, you get diabetes. In an unexpected finding, scientists have identified four viruses that can produce insulin-like hormones that are active on human cells. The discovery brings new possibilities for revealing biological mechanisms that may cause diabetes or cancer.READ MORE
Pre-Clinical Safety in Cancer Drug Development: “Attitude to Safety Needs to Change”News
Many companies involved in cancer drug research and development need to re-think their use of safety data in helping to bring new drugs to cancer patients.
Dr Richard Knight of ApconiX will tell this month’s conference, that greater focus on pre-clinical safety should be fundamental to the development of new cancer therapies.
Comments | 0 ADD COMMENT
4th International Conference on Crystallography & Novel Materials
Nov 19 - Nov 20, 2018