Pore-forming toxins (PFT) are common bacterial poisons. They attack organisms by introducing holes in cell membranes. A team of scientists has now unraveled the mechanism of action for one of these toxins.
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. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, with unknown structures. YaxAB was shown to be cytotoxic and likely involved in pathogenesis, though the molecular basis for its two-component lytic mechanism remains elusive.
Scientists all over the world are trying to understand how these toxins produce the fatal openings in cell membranes in hope of one day inhibiting the pathogenic, pore-forming poisons.
After several years of research, an interdisciplinary team managed to elucidate the mode of action of a toxin subspecies in which two components interact to develop the deadly effect. Authors in the journal Nature Communications present crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of the YaxAB complex.
The structures reveal a pore predominantly composed of decamers of YaxA–YaxB heterodimers. Both subunits bear membrane-active moieties, but only YaxA is capable of binding to membranes by itself. YaxB can subsequently be recruited to membrane-associated YaxA and induced to present its lytic transmembrane helices. Pore formation can progress by further oligomerization of YaxA–YaxB dimers.
"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 the author. "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.
https://www.tum.de/en/about-tum/news/press-releases/detail/article/34629/
http://www.nature.com/articles/s41467-018-04139-2
How pore forming toxins act on membranes?
- 2,757 views
- Added
Edited
Latest News
Wiring of the human neocortex
By newseditor
Posted 24 Apr
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Other Top Stories
A protein that promotes brain metastasis identified!
Read more
Hypoxic memory promotes tumor spread!
Read more
Glutamine-blocking drug slows tumor growth and strengthens anti-tum…
Read more
Long non-coding RNA in childhood brain cancer!
Read more
Astronauts prep may help multisystem toxicity in cancer patients
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Harnessing gastrointestinal…
By newseditor
Posted 24 Apr
Sex-specific modulation of…
By newseditor
Posted 24 Apr
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar