Höppner Lab

Research Projects

The research group of Dr. Höppner deals with structural biology of proteins and the in vitro characterization of proteases. A particular focus is on the SPP/SPPL proteases. With their catalytic sites located in the hydrophobic regions of cellular membranes these proteases cleave their substrates within this region. However, the enzymes also have hydrophilic domains both intracellularly and extracellularly. Its our primary goal to elucidate the interaction of these different domains in relation to substrate recognition and regulation.

3D Structure of SPP/SPPL Proteases

Hoeppner et al., FEBS, Oct2023, doi:10.1111/febs.16968
Experimental 3D structures are currently not available for mammalian SPP/SPPL proteases. Research into these proteases is therefore still based exclusively on AI-generated predictions. Thus, to understand their unique features, elucidating the structural details of SPP/SPPL proteases is crucial. In addition, the knowledge of experimentally determined high-resolution 3D structures forms the basis for structure-based drug development and for a comprehensive understanding of substrate recognition and cleavage mechanisms. In the future, knowledge of the 3D structures will facilitate the identification of substrates, provide insight into the molecular cleavage mechanisms and the physiological functions of this protease family.

SPP/SPPL in vitro cleavage

The representatives of the SPP/SPPL protease family are intramembrane aspartyl proteases, which, similar to presinilins, cleave their transmembrane substrates within the hydrophobic membrane regions and are involved in various pathophysiological processes. However, identifying substrates and understanding cleavage mechanisms are major challenges.

Therefore, our goal is to develop assay systems that allow in vitro characterization of the SPP/SPPL proteases and enable unrestricted investigation of substrate recognition and enzymatic kinetics. In the future, these assay systems will contribute to the identification of complex partners, the confirmation of substrates, mutagenesis studies and the characterization of inhibitors. This will help to decipher complex molecular interactions, advance drug development, and promote a comprehensive understanding of enzyme functions in a controlled environment.

Funding

Intramural Research Funding, project funding, Medical faculty of the University of Augsburg – Funding since 2023

Publications

2023 | 2009 | 2006 | 2005

2023

Hoeppner Sabine, Schröder Bernd, Fluhrer Regina. Structure and function of SPP/SPPL proteases: insights from biochemical evidence and predictive modeling. https://doi.org/10.1111/febs.16968
PDF | BibTeX | RIS | DOI

2009

Godemann Robert, Madden James, Krämer Joachim, Smith Myron, Fritz Ulrike, Hesterkamp Thomas, Barker John, Höppner Sabine, Hallett David, Cesura Andrea, Ebneth Andreas, Kemp John. Fragment-based discovery of BACE1 inhibitors using functional assays. https://doi.org/10.1021/bi901061a
PDF | BibTeX | RIS | DOI

2006

Larivière Laurent, Geiger Sebastian, Hoeppner Sabine, Röther Susanne, Sträßer Katja, Cramer Patrick. Structure and TBP binding of the Mediator head subcomplex Med8–Med18–Med20. https://doi.org/10.1038/nsmb1143
PDF | BibTeX | RIS | DOI

2005

Baumli Sonja, Hoeppner Sabine, Cramer Patrick. A conserved mediator hinge revealed in the structure of the MED7·MED21 (Med7·Srb7) heterodimer. https://doi.org/10.1074/jbc.m413466200
PDF | BibTeX | RIS | DOI
Meinhart Anton, Kamenski Tomislav, Hoeppner Sabine, Baumli Sonja, Cramer Patrick. A structural perspective of CTD function. https://doi.org/10.1101/gad.1318105
PDF | BibTeX | RIS | DOI
Hoeppner Sabine, Baumli Sonja, Cramer Patrick. Structure of the Mediator subunit cyclin C and its implications for CDK8 function. https://doi.org/10.1016/j.jmb.2005.05.041
PDF | BibTeX | RIS | DOI
Höppner Christoph, Carle Anna, Sivanesan Durga, Hoeppner Sabine, Baron Christian. The putative lytic transglycosylase VirB1 from Brucella suis interacts with the type IV secretion system core components VirB8, VirB9 and VirB11. https://doi.org/10.1099/mic.0.28326-0
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