A small molecule inhibits jasmonic acid and helps to explain its effects
Researchers trying to get new information about the metabolism of plants can switch off individual genes and study the resulting changes. However, Erich Kombrink from the Max Planck Institute for Plant Breeding Research in Cologne and Markus Kaiser from the University of Duisburg-Essen adopt a different approach.
Jarin1 inhibits the enzyme JAR1 by displacing the natural substrate, Jasmonoyl-isoleucine (JA-Ile), from its binding site. Both substances overlap, so that JAR1 can no longer fulfil its tasks. The left panel shows an overview of the entire enzyme; the right panel a view into the active centre.
© Corey S. Westfall, Washington University, St. Louis
They identify small molecules that block specific components of the metabolic process like brake pads and prevent the downstream reactions. In their search for these molecules, they use a biological selection process involving intact plants. This strategy has long been exploited in drug research. Its application in the plant sciences, however, is relatively new.
Kombrink, Kaiser and their colleagues have identified a molecule that interferes with the effect of jasmonic acid. This plant hormone influences flower formation, root growth, defence against herbivores and infections, wound healing, ageing of plants, and much more.
Although many questions about plant metabolism can be answered through targeted gene mutations, the method has its limits. This is also demonstrated in the case of jasmonic acid and its derivatives. So far, only one signalling chain has been discovered, but this cannot explain the wide-ranging effect of this plant hormone. Therefore, other hitherto undiscovered signalling paths and action mechanisms must exist.
To find out more about them, Kombrink and Kaiser have adopted an approach that is similar to one used in medicine. Their strategy is based on the blocking of important metabolic pathways using low molecular weight compounds, which are easily assimilated by the plant. While in medical therapy such compounds are assimilated through the blood, in the plant they are introduced through the root.
The scientists embarked on their search with a screening of Arabidopsis thaliana and treating the plants with compounds in such a way that the desired selection could be identified by a conspicuous trait. Of the 1728 substances from a commercial compound library tested 16 emerged as inhibitors.
This number was further reduced using more selective tests. In the end, only one substance turned out to be a specific inhibitor of the jasmonic acid signalling pathway and was given the name Jarin-1. “In terms of its basic structure, the substance is a plant alkaloid, whose two amino groups can carry different side chains,” Kombrink explains. “However, its effect is associated with a particular side chain in one of the positions. Other side chains impair the activity of the substance. We also deliberately synthesised it once again to be certain that we had understood its chemical structure correctly.”
The scientists also looked for the target of the newly discovered inhibitor. The known signalling chain starts with the conjugation of the jasmonic acid with the amino acid isoleucine by an enzyme called JAR1. The resulting pair leads to the expression – following various detours – of the genes necessary for the relevant effect of the jasmonic acid. Kombrink and Kaiser were able to show that JAR1 is the target of the newly discovered inhibitor. Due to the inhibition, the jasmonic acid conjugated with isoleucine does no longer accumulate in the cell. As a result genes are not expressed because the jasmonic acid–isoleucine pair no longer activates the genes’ starting point.
The Jarin-1 inhibitor identified by Kombrink and Kaiser not only works in Arabidopsis but also in Cardamine hirsuta or hairy bittercress. “So we are obviously dealing with a broadly applicable molecule,” comments Kombrink. Under the effect of the inhibitor, the plants show the same features as they do following the targeted mutation of genes from the jasmonic acid signalling pathway.
The scientists also investigated the exact location where the molecule takes effect. They succeeded in demonstrating that it binds to the active centre of JAR1 and inhibits the natural substrate. “Our molecule is not a classical competitive inhibitor,” says Kombrink. “But its effect can be explained, at least in parts, by displacement of the substrate from its binding site.”
Small molecules are interesting new tools for plant research. Through their work, the researchers show how it is possible to search for them systematically and to identify their molecular mode of action.
Dr. Erich Kombrink | Max-Planck-Institute
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering