Research
Characterization of the mechanism of production of botulinum toxin
[Credits: Adapted from Nucleic Acids Research 2018]
17 May 2018
Towards the mechanism behind botulin toxin production

The team led by Ramón y Cajal researcher Marian Oliva, from the Department of Structural and Chemical Biology at the Centro de Investigaciones Biológicas, in collaboration with the group of Dr. Fernando Moreno Herrero of the National Biotechnology Center and the team of the emeritus researcher Ramón Díaz Orejas, also from CIB, has recently published in the journal Nucleic Acids Research the mechanism by which the first steps in the distribution of certain "toxic DNA" in bacteria occur.

The bacterium Clostridium botulinum contains small molecules of DNA necessary to produce botulinum toxin, lethal in infectious processes, but at the same time widely applied in the sanitary and aesthetic world. It is known that these DNA molecules include their own machinery for maintenance during bacterial growth and proliferation, but how this process began was not known.

In this article, co-financed with FEDER funds, Martín-García et al. explain how the TubR protein is responsible for folding the "toxic DNA" at two different points of its structure to achieve the formation of a double ring, an architecture that until now had never been observed. This structure, called segrosome, is key in the next distribution step, where a motor protein called TubZ is anchored to move the genetic material to different points in the cell. Evidence has also been obtained about the involvement of the segrosome in the transcriptional regulation of the system itself. The location of these points of union of the TubR protein has been achieved by means of the combination of different structural techniques, such as electron microscopy and atomic force microscopy, that have been key to decipher how this interaction is able to give rise to this unique architecture. In addition, the technique of magnetic tweezers allowed to study the process of formation of the double ring in real time and revealed the coupling of the segrosome with the super-coiling of other regions of the same DNA. This could have implications in the packaging of the DNA to facilitate its transport.

The knowledge of the mechanism by which these molecules are organized and maintained in different bacterial strains is important for the development of control measures against virulent bacteria.

 

Reference: The TubR-centromere complex adopts a double-ring segrosome structure in Type III partition systems. Bárbara Martín-García, Alejandro Martín-González, Carolina Carrasco, Ana M. Hernández-Arriaga, Rubén Ruíz-Quero, Ramón Díaz-Orejas, Clara Aicart-Ramos, Fernando Moreno-Herrero, María A. Oliva.
Nucleic Acids Research 2018. https://doi.org/10.1093/nar/gky370

 

More info: CNB Press Release