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Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.
[Credit: Technical University of Munich, TUM] |
Furthermore the researchers discovered that another human protein, thioredoxin, is able to activate beta-defensin 1 even in the presence of oxygen. Moritz Marcinowski and Professor Johannes Buchner from the Department of Chemistry at the Technical University of Munich, used circular dichroism spectroscopy to elucidate the differences between the folded inactive and the unfolded active form of the protein.
Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.
So far the cause of inflammatory bowel disease is unclear. Genetic as well as environmental factors seem to play a role, finally leading to a weakening of the antimicrobial barrier, which is mainly mediated by defensins. Accordingly the identified mechanism might contribute to the development of new therapies to treat affected patients.
The presented work is the result of a cooperation project with six participating centers, led by Emmy Noether junior research group leader Dr. Jan Wehkamp. In addition to five researchers from Stuttgart (Dr. Margarete Fischer-Bosch-Institute for Clinical Pharmacology and the Robert Bosch-Hospital (Bjoern Schroeder, Sabine Nuding, Julia Beisner, Eduard Stange and Jan Wehkamp) the Department of Dermatology at University of Tübingen (Martin Schaller), the Max-Planck-Institute for Developmental Biology in Tübingen (Sandra Groscurth), the Department of Dermatology at University of Kiel (Zhihong Wu), as well as the Department of Chemistry at the Technische Universitaet Muenchen (Moritz Marcinowski and Johannes Buchner) were involved. The work was funded by the Deutsche Forschungsgemeinschaft (Emmy Noether-Program for young researchers, Cluster of Excellence Center for Integrated Protein Science Munich) and by the Robert- Bosch-Foundation.