Proteins are responsible for nearly every essential process of life. Their form and structure are of crucial importance for their functionality.
Scientists at the Max Planck Institute of Biochemistry (MPIB) have recently discovered a so far unknown sequence of reactions which is necessary for newly generated proteins to acquire their correct structure.
„In the mechanism we found, the folding is accomplished in a number of fast intermediate steps rather than in one single block“, explains Manajit Hayer-Hartl, MPIB research group leader. „Because this mode of action is energetically more favorable, the proteins are folded not only correctly, but also much faster than previously assumed.“
Proteins are the workhorses of the cell and thus responsible for almost all biological functions including metabolism, signal transmission or the determination of the cell’s shape. However, before they can fulfill their various tasks, the chain-like molecules must first adopt an intricate three-dimensional conformation. This process is called protein folding and is one of the most important processes in biology.
In fact, in the event of improper folding, proteins are often no more able to carry out their duties, or even tend to clump together in aggregates. This in turn can lead to severe diseases like Alzheimer’s or Parkinson’s. In order to avoid this, specialized proteins, the so-called chaperones, help other proteins to adopt their proper shape.
The bacterial chaperones GroEL and GroES serve as an example for this principle: together, they build up a cage-like structure in which they encapsulate new, not yet folded proteins, thereby al-lowing them to fold properly. However, the exact way in which this is accomplished has so far been unclear and is a research topic of the MPIB team led by Manajit Hayer-Hartl and F. Ulrich Hartl, in collaboration with John Engen from Northeastern University in Boston.
Active acceleration of folding
„Our results demonstrate that the chaperones not only prevent protein clumping, but also dramatically accelerate the folding process”, explains Florian Georgescauld, scientist at the MPIB. „Surprisingly, the chaperones achieve this by changing the mechanism of folding: Instead of folding in one large single block, the protein gets its final structure in a series of small, rapid steps – like an elaborate high-speed Origami.” The researchers think that splitting up the reaction might render it energetically more favorable, which in turn would lead to increased speed. Hence, the folding process is finished in a few seconds rather than in several minutes.
The study shows for the first time that chaperones can act not only passively, by preventing aggregation, but as an active folding cage that catalyzes the folding process. This results in a high-speed folding mechanism which is of particular biological relevance, so the researchers say, since in this way proteins can be folded faster than they are produced. Thus, a backlog of proteins which are not yet or improperly folded and the disastrous consequences which might go along with this can be avoided.
F. Georgescauld, K. Popova, A. J. Gupta, A. Bracher, J. R. Engen, M. Hayer-Hartl and F. U. Hartl: GroEL/ES Chaperonin Modulates the Mechanism and Accelerates the Rate of TIM-Barrel Domain Folding. Cell, May 8, 2014.
Dr. Manajit Hayer-Hartl
Chaperonin-assisted Protein Folding
Max Planck Institute of Biochemistry
Am Klopferspitz 18
http://www.biochem.mpg.de/news/ueber_das_institut/forschungsbereiche/strukturforschung/hayer_hartl_press - Press Page of the Research Group "Chaperonin-assisted Protein Folding" (Manajit Hayer-Hartl)
http://www.biochem.mpg.de/en/rg/hayer-hartl - Website of the Research Group "Chaperonin-assisted Protein Folding" (Manajit Hayer-Hartl)
Anja Konschak | Max-Planck-Institut
Two decades of training students and experts in tracking infectious disease
27.11.2015 | Hochschule für Angewandte Wissenschaften Hamburg
Increased carbon dioxide enhances plankton growth, opposite of what was expected
27.11.2015 | Bigelow Laboratory for Ocean Sciences
Planet Earth experienced a global climate shift in the late 1980s on an unprecedented scale, fuelled by anthropogenic warming and a volcanic eruption, according to new research published this week.
Scientists say that a major step change, or ‘regime shift’, in the Earth’s biophysical systems, from the upper atmosphere to the depths of the ocean and from...
The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...
Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.
In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...
In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.
Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...
Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...
25.11.2015 | Event News
17.11.2015 | Event News
21.10.2015 | Event News
27.11.2015 | Press release
27.11.2015 | Life Sciences
27.11.2015 | Materials Sciences