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
New technology helps ID aggressive early breast cancer
01.07.2016 | University of Michigan Health System
In times of great famine, microalgae digest themselves
01.07.2016 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung
Densified regions with drastically reduced internal motion either act as crystal precursors or cluster and frustrate all further dynamics
Glasses are neither fluids nor crystals. They are amorphous solids and one of the big puzzles in condensed matter physics. For decades, the question of how...
Since the completion of the human genome an important goal has been to elucidate the function of the now known proteins: a new molecular method enables the investigation of the function for thousands of proteins in parallel. Applying this new method, an international team of researchers with leading participation of the Technical University of Munich (TUM) was able to identify hundreds of previously unknown interactions among proteins.
The human genome and those of most common crops have been decoded for many years. Soon it will be possible to sequence your personal genome for less than 1000...
3D printing revolutionized the manufacturing of complex shapes in the last few years. Using additive depositing of materials, where individual dots or lines...
R2D2, a joint project to analyze and development high-TRL processes and technologies for manufacture of flexible organic light-emitting diodes (OLEDs) funded by the German Federal Ministry of Education and Research (BMBF) has been successfully completed.
In contrast to point light sources like LEDs made of inorganic semiconductor crystals, organic light-emitting diodes (OLEDs) are light-emitting surfaces. Their...
High resolution rotational spectroscopy reveals an unprecedented number of conformations of an odorant molecule – a new world record!
In a recent publication in the journal Physical Chemistry Chemical Physics, researchers from the Max Planck Institute for the Structure and Dynamics of Matter...
30.06.2016 | Event News
28.06.2016 | Event News
09.06.2016 | Event News
01.07.2016 | Physics and Astronomy
01.07.2016 | Earth Sciences
01.07.2016 | Medical Engineering