During his studies, Zebin Hong emphasized on the natural mechanisms for activity regulation of the type-II transmembrane serine protease matriptase. In general, the proteolytic activity of matriptase is highly regulated via the maturation of the zymogen form and by inhibition by its natural inhibitors. Hepatocyte Growth Factor Activator Inhibitor-1 (HAI-1) is an important inhibitor of matriptase. Both matriptase and HAI-1 has been shown in mouse knock out models to be essential for life. Moreover, a balanced level between matriptase and HAI-1 appears to be decisive for maintaining homeostasis. Importantly, it has also been shown in mice genetic studies that excessive matriptase activity relative to HAI-1 in most cases results in the development of cancer.

Zebin Hong determined the NMR solution structure of the uncharacterized MANEC domain, the N-terminal domain of Hepatocyte Growth Factor Activator Inhibitor 1 (HAI-1), a first structure of its kind of a MANEC-type domain. Zebin Hong also solved the X-ray crystal structure of the second domain of HAI-1, the ‘internal domain’, and proved it to be a stimulator of HAI-1 inhibitory activity. These two structures not only provide the missing structural information on HAI-1 domains needed for future computational approaches to model full-length HAI-1 but reveal exciting insights to the interplay between tertiary structure and function of this multidomain protein.

The PhD degree was completed at iNANO and the Department of Molecular Biology and Genetics, Science and Technology, Aarhus University.

This resume is prepared by the PhD student.

Time: Thursday 10 September 2015 at 13.15
Place: Building 1590, room 213, iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C
Title of dissertation: Structural insights to the natural mechanisms for activity regulation of matriptase
Contact information: Zebin Hong, e-mail: zebin@inano.au.dk, tel.: +45 5019 9107
Members of the assessment committee:
Professor Vincent Ellis, School of Biological Sciences, University of East Anglia, UK
Professor Birte Svensson, Department of Systems Biology, Technical University of Denmark
Associate Professor Rikke Louise Meyer (chair), Department of Bioscience and iNANO, Aarhus University
Main supervisor:
Associate professor Jan Kristian Jensen, Department of Molecular Biology and Genetics, the Danish-Chinese Center for Proteases and Cancer, Aarhus University
Co-supervisor:
Associate Professor Frans Mulder, Department of Chemistry and iNANO, Aarhus University
Language: The PhD dissertation will be defended in English.

The defence is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1521, room 112, 8000 Aarhus C.