Until recently, it was only known that TccC3 transfers an ADP-ribose group to actin promoting its aberrant polymerization, which leads to actin filament clumping. "For a long time, we struggled with obtaining a complete picture of the intoxication process, since we lacked the structural data of the secreted enzymes, one of which is TccC3", reflects Raunser. Setting up the opponent by reducing the striking distance There, it unfolds its deadly effect by disturbing the regulation of the cell's cytoskeleton, which consists of a network of polymerized actin (F-actin) filaments involved in many essential cellular processes.
The scientists showed that the subunits of the Tc toxin complex work together like a syringe (link to former press release)): once the subunits are assembled, structural changes in the complex trigger the opening of a cocoon which contains a toxic enzyme, which is then secreted in a unique injection mechanism via a channel into the host cell (link). Unraveling the structure of the Tc toxin subunits and their assembly by cryo electron microscopy (cryo-EM) enabled us to understand the key steps of toxin activation and membrane penetration", The mechanism of action of Tc toxins has only recently been uncovered to a greater extent by the work of Stefan Raunser's team in structural biology at the MPI Dortmund. A bacterial syringe delivers a deadly enzyme No less complex and in fact very effective is the intoxication process of toxin complexes (Tc), virulence factors of many bacteria, including insect and human pathogens.
As simple as it may seem, this process is in fact a sophisticated and multi-staged procedure. The toxin unfolds its lethal effect by preventing the release of neurotransmitters at the point where nerve cells attach to muscles, thereby paralyzing them.
Only one-thousandth of a milligram of the bacterial botulinum toxin is necessary to kill a living organism. Their findings not only reveal how the deadly cargo of the Tc toxin drives the collapse of the cell’s cytoskeleton but provide an explanation of the toxin’s high efficiency. In order to unravel the details behind the infection mechanism of Tc toxins in particular, experts in cryo-EM and protein-NMR from Stefan Raunser’s group at the Max Planck Institute of Molecular Physiology (MPI) in Dortmund and Hartmut Oschkinat’s group from the Leibniz Forschungsinstitut für Molekulare Pharmakologie in Berlin have worked side by side. Bacterial toxins hit host organisms where it hurts most, promoting infection and diseases in animals and humans. Aug 3 2022Ī harmful and often deadly substance made by bacteria, a bacterial toxin manipulates host cell functions and disrupts vital cell processes in a living organism.
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