How the NLRP3 danger sensor stretches like a thread – Fauna and Flora News

Redness, swelling, pain – these are signs of inflammation. It serves to protect the body against pathogens or foreign substances. Researchers from the universities of Bonn and Cologne were able to show that the inflammatory reactions of an important sensor protein take place in a specific spatial direction. This discovery has the potential to stop inflammation at the “growing end” and thus put an end to chronic inflammatory diseases. The study has just been published in the journal Scientists progress. »

If bacteria or viruses attack living cells or other foreign substances appear there, the danger sensor with the abbreviation NLRP3 is activated. “Protein deposits in the brain that are characteristic of Alzheimer’s disease, so-called amyloid-ß plaques, can also trigger NLRP3,” says Professor Matthias Geyer from the Institute for Structural Biology at University Hospital Bonn. , referring to previous studies. As these previous studies by the researchers show, this reaction is increasingly self-reinforcing: the inflammatory reaction triggered by NLRP3 promotes the further deposition of amyloid-ß plaques and contributes significantly to the disease process.

Once activated, several NLRP3 proteins attach to each other and thus form the core of a thread-like structure on which more and more proteins gather. “The reaction starts when about a dozen NLRP3 molecules are present,” reports Geyer. In theory, an infinite number of NLRP3 molecules can join together and extend the thread-like structure – scientifically called “filament” – further and further. Inga Hochheiser from Professor Geyer’s team has now been able to show the direction in which this filament develops and continues to develop. “We were able to obtain this information using cryo-electron microscopy. This method makes it possible to observe protein molecules with a magnification of up to 80,000 times and thus make them directly visible,” explains Hochheiser.

“Still image” of the filiform structure under the microscope

In small steps, the scientist sprinkled NLRP3 isolated from cells onto a sample holder and froze this mixture. This provided the researchers with a sort of “still image” under the cryo-electron microscope. The emergent threadlike structure of NLRP3 molecules arranged side by side was thus visualized. “These individual images made it possible to understand how the filaments lengthen, like in a film,” explains Hochheiser. As the molecules fall differently on the sample holder when they are sprinkled, they can be seen from different perspectives under the microscope. These different views can be combined on the computer to create a three-dimensional image. The results showed that the filaments only form in one direction. “This allowed us to visualize part of the inflammatory apparatus and literally read the direction of growth”, explains Professor Geyer, who led the study and is a member of the ImmunoSensation2 Center of Excellence and the Research Domain Transdisciplinary “Life and Health” at the University of Bonn.

Stopping chronic inflammatory diseases

“The technical challenge was to find the transitions in the threadlike structures and make them visible in the image,” explains Professor Elmar Behrmann from the Institute of Biochemistry at the University of Cologne. “The new findings now allow us to target the rising end of the inflammatory response using antibodies or drugs,” says Hochheiser. This brings the researchers closer to their goal of stopping further buildup of the inflammatory apparatus and thereby thwarting chronic inflammation.

Participating Institutions and Funding:

In addition to the Institute for Structural Biology and the Institute for Innate Immunity at the University Hospital Bonn, the Institute for Biochemistry at the University of Cologne and the Walter and Eliza Hall Institute for Medical Research in Melbourne (Australia) are involved in the study. Measurements were carried out at the Caesar Research Center in Bonn and at the Rudolf Virchow Center at the University of Würzburg. The study was funded by the Else Kröner-Fresenius Foundation and the German Research Foundation.

Source of the story:

Materials provided by University of Bonn. Note: Content may be edited for style and length.

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How the NLRP3 danger sensor stretches like a thread – Fauna and Flora News


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