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
The herbivore dilemma: How corn plants fights off simultaneous attacks
09.02.2016 | Boyce Thompson Institute for Plant Research
Shedding Light on Bacteria
09.02.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels
A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...
Indications of light-induced lossless electricity transmission in fullerenes contribute to the search for superconducting materials for practical applications.
Superconductors have long been confined to niche applications, due to the fact that the highest temperature at which even the best of these materials becomes...
Researchers at King’s College London and the Wellcome Trust Sanger Institute in the United Kingdom have for the first time demonstrated a direct link between the Wbp2 gene and progressive hearing loss. The scientists report that the loss of Wbp2 expression leads to progressive high-frequency hearing loss in mouse as well as in two clinical cases of children with deafness with no other obvious features. The results are published in EMBO Molecular Medicine.
The scientists have shown that hearing impairment is linked to hormonal signalling rather than to hair cell degeneration. Wbp2 is known as a transcriptional...
Pollens, the bane of allergy sufferers, could represent a boon for battery makers: Recent research has suggested their potential use as anodes in lithium-ion batteries.
"Our findings have demonstrated that renewable pollens could produce carbon architectures for anode applications in energy storage devices," said Vilas Pol, an...
Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...
09.02.2016 | Event News
02.02.2016 | Event News
26.01.2016 | Event News
09.02.2016 | Event News
09.02.2016 | Materials Sciences
09.02.2016 | Power and Electrical Engineering