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Yersinia plague bacterium |
Yersinia
have spread fear and terror, especially in the past, but today the plague
pathogens have still not been completely eradicated. The bacteria inject
various enzymes, including the enzyme YopO, into the macrophages of the immune
system. There it is activated and prevents the defense cells from enclosing and
digesting the plague bacteria. Using the latest methods, scientists from the
Institute of Physical and Theoretical Chemistry at the University of Bonn have
now deciphered how YopO changes its shape and thus contributes to confusing the
immune system. The results have now been published in the journal Structure.
The
structural biologist has already done research in Yersinia as a PhD student at
the Helmholtz Centre for Infection Research in Braunschweig. The special
feature of the plague pathogens is a kind of syringe with which they inject the
YopO and some other enzymes into the macrophages of the immune system. However,
YopO only becomes active when it binds to the actin of the scavenger cell.
Normally, the structural protein actin helps the phagocyte to form protrusions
with which it flows around the pathogens and then disolves them into small
pieces. During this process, the macrophage calls for help from other defense
cells.
The
scientists at the University of Bonn therefore used several instruments from
the structural elucidation toolbox. Together with Dr. Dmitri Svergun from the
European Molecular Biology Laboratory in Hamburg, they used the PETRA III
electron accelerator of the German Electron Synchrotron DESY. "The
extremely intense and focused X-rays can be used to study the overall structure
and structural changes of enzymes dissolved in water with the aid of
small-angle X-ray scattering," said Svergun.
In
addition, the researchers attached spin markers to certain positions of YopO
and actin. These function like survey points in the landscape at which, for
example, the exact location of a property can be determined. "Using the
spin markers, we can use a molecular ruler -- the PELDOR method -- to measure
the nanometer distances between these positions and thus determine how YopO and
actin change shape," reports Hagelüken. So far it has been presumed that
YopO performs a folding movement like scissors as soon as it binds to actin.
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Posted by Dr. Tim Sandle, Pharmaceutical Microbiology
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