Pore-forming toxins are common bacterial poisons. They attack organisms by opening holes in cell membranes. A team of scientists at the Technical University of Munich (TUM) has now unraveled the mechanism of action for one of these toxins. The findings could help combat associated diseases and protect plants from damage.
Pore-forming toxins are bacterial poisons that destroy cells by creating holes in the cell membranes. Many bacterial pathogens produce such toxins, including, for example, some strains of the intestinal bacterium Escherichia coli as well as Yersinia enterolitica, a pathogen related to the plague. With the help of their toxins they attack all kinds of organisms – from plants to insects, and even humans.
Scientists all over the world are trying to understand just how these toxins produce the fatal holes in cell membranes in the hope of one day inhibiting the pathogenic, pore-forming poisons.
Now an interdisciplinary team from the Technical University of Munich has managed to elucidate the mode of action of a subspecies of the toxin class in which two components interact to develop the deadly effect.
Two partners with lethal impact
Combining crystallographic and cryo-electron microscopy methods, Bastian Bräuning and Professor Michael Groll from the Department of Biochemistry, in collaboration with Eva Bertosin and Professor Hendrik Dietz from the Department of Experimental Biophysics, managed to shed light upon the precise molecular structures of the soluble individual components, as well as the pore complex.
"We determined that only one of the two components is able to bind to the membrane. In a second step it recruits the other component and the base domains of two proteins together form the basic pore unit," explains Bastian Bräuning. "This is a new kind of mechanism from which we can obtain much useful insight."
The structure of the resulting hole in the cell membrane resembles a crown, whose teeth comprise 40 subunits of the two interacting partners.
One mechanism – myriad potential applications
The team of researchers lead by Bräuning and Groll investigated the interaction of the two partner proteins in the toxins of Yersinia enterolitica and Photorhabdus luminescens, a bacterium that lives in nematodes: together, they attack susceptible insect hosts. The latter is thus interesting as an insecticide.
The new insight moves the development of substances that inhibit the interaction of the two components, and thus prevent the formation of pores, into the realm of the conceivable.
"Our combination of crystallography and cryo-electron microscopy was key to understanding the necessity of the two-component construction of the toxin from a biochemical perspective," explains Professor Michael Groll. "This insight will also help us understand more complex variants in the future, for example those in which three components work together."
Bastian Bräuning, Eva Bertosin, Florian Praetorius, Christian Ihling, Alexandra Schatt, Agnes Adler, Klaus Richter, Andrea Sinz, Hendrik Dietz and Michael Groll
Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB
Nature Communications, vol. 9, 1806 (2018) – DOI: 10.1038/s41467-018-04139-2
The work is the result of close a cooperation between the professors of Biochemistry and Biophysics at the Technical University of Munich. Both working groups are part of the Cluster of Excellence Center for Integrated Protein Science Munich (CIPSM). The results were validated by the Department of Pharmaceutical Chemistry and Bioanalytics at the Institute of Pharmacy of the Martin-Luther University Halle-Wittenberg. The X-ray structure data were collected at the synchrotron light source of the Paul Scherrer Institute (Villigen, Switzerland).
Prof. Michael Groll
Technical University of Munich
Chair of Biochemistry
Tel.: +49 89 289 13361
https://www.tum.de/nc/en/about-tum/news/press-releases/detail/article/34629/ Link to the press release
Dr. Ulrich Marsch | Technische Universität München
Münster University chemists create new types of Lewis acids on the basis of phosphorus
22.10.2019 | Westfälische Wilhelms-Universität Münster
Obesity risk quantification:a jump towards the future through the artificial intelligence lens applied to lipid science
22.10.2019 | Technische Universität Dresden
Researchers have succeeded in creating an efficient quantum-mechanical light-matter interface using a microscopic cavity. Within this cavity, a single photon is emitted and absorbed up to 10 times by an artificial atom. This opens up new prospects for quantum technology, report physicists at the University of Basel and Ruhr-University Bochum in the journal Nature.
Quantum physics describes photons as light particles. Achieving an interaction between a single photon and a single atom is a huge challenge due to the tiny...
A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)
It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...
Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.
The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...
Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.
Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...
A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.
The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
22.10.2019 | Materials Sciences
22.10.2019 | Medical Engineering
22.10.2019 | Power and Electrical Engineering