Structure and Mechanism of an Aspartimide-Dependent Peptide Ligase in Human Legumain
Elfriede Dall, Julia C. Fegg, Peter Briza, and Hans Brandstetter
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Abstract: Peptide ligases expand the repertoire of genetically encoded protein architectures by synthesizing new peptide bonds, energetically driven by ATP or NTPs. Here, we report the discovery of a genuine ligase activity in human legumain (AEP) which has important roles in immunity and tumor progression that were believed to be due to its established cysteine protease activity. Defying dogma, the ligase reaction is independent of the catalytic cysteine but exploits an endogenous energy reservoir that results from the conversion of a conserved aspartate to a metastable aspartimide. Legumains dual protease–ligase activities are pH- and thus localization controlled, dominating at acidic and neutral pH, respectively. Their relevance includes reversible on–off switching of cystatin inhibitors and enzyme (in)activation, and may affect the generation of three-dimensionalMHCepitopes. The aspartate– aspartimide (succinimide) pair represents a new paradigm of coupling endergonic reactions in ATP-scarce environments.
The open access article can be found  here  
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Hedgehog/GLI and PI3K signaling in the initiationand maintenance of chronic lymphocytic leukemia
D. Kern, G. Regl, S.W. Hofbauer, P. Altenhofer, G. Achatz, A. Dlugosz, H. Schnidar, R. Greil,
T.N. Hartmann and F. Aberger
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Abstract: The study addressed the role of Hedgehog (HH)/GLI and its putative interaction with the PI3K/AKT cascade in the initiation and maintenance of chronic lymphocytic leukemia (CLL). Using transgenic mouse models, we show that HH/GLI signaling alone or in combination with PI3K/AKT does not suffice to initiate a CLL-like phenotype. By contrast, our work identifies a critical role of GLI and PI3K signaling for the survival of human primary CLL cells, and further shows that combined targeting of GLI and PI3K/AKT/mTOR signaling has a synergistic therapeutic effect. The data provide a basis for rational combination therapies targeting HH/GLI and PI3K signaling in this common hematopoietic malignancy.
The open access article can be found  here
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Fold-stability during endolysosomal acidification is a key factor for allergenicity and   Immunogenicity of the major birch pollen allergen
Yoan Machado, Regina Freier, Sandra Scheiblhofer, Theresa Thalhamer, Melissa Mayr, Peter Briza, Sarina Grutsch, Linda Ahammer, Julian E. Fuchs, Hannes G. Wallnoefer, Almedina Isakovic, Vera Kohlbauer, Arthur Hinterholzer, Markus Steiner, Martin Danzer, Jutta Horejs-Hoeck, Fatima Ferreira, Klaus R. Liedl, Martin Tollinger, Peter Lackner, Christopher M. Johnson, Hans Brandstetter, Josef Thalhamer and Richard Weiss
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Abstract: The search for intrinsic factors, which account for a protein’s capability to act as an allergen, is ongoing. Here we show for the first time how structural stability of a protein contributes to allergic sensitization. This knowledge opens the door to rational molecular design of novel therapeutics and vaccines.
The open access article can be found  here
PRIZE: € 100,00  
CONGRATULATIONS!