Cel To understand how molecular machines execute their function, a multidisciplinary approach combining structural biology with biochemical and computational studies is required. In this project, I will couple these three methodologies to understand the dynamic interactions and regulatory mechanisms of the 26S proteasome by cryo-EM single particle analysis.Recent work from our lab and others resulted in a pseudo-atomic structure of the 26S proteasome. At the same time, cryo-EM technology has been revolutionized by automated data acquisition schemes and new electron detectors, which empower us to explore dynamic structures at high resolution. Thus, now we can not only “watch” conformational changes in macromolecules as they perform their function, but also structurally analyze their transient interactions. In the case of the 26S proteasome, binding of both proteasome interacting proteins (PIPs) and ubiquitylated substrates is crucial for proteasome assembly and function, but how these interactions occur remains poorly understood.The major goals of this proposal will be to 1) understand the functional and structural interactions of the proteasome and various PIPs, and 2) how the proteasome recognizes different ubiquitylated substrates through different ubiquitin receptors. These results will contribute not only to the general understanding of proteasome regulation, but also to deciphering the code of ubiquitin signaling employed in various cellular pathways, thus impacting different areas of biochemistry, molecular biology and cell biology. Furthermore, this will be the first systematic exploration of a structural “interactome”, which may pave the way for further studies on other macromolecules. Finally, given the role of the proteasome in numerous human diseases, a detailed knowledge of the molecular mechanisms for its regulation can also have significant biomedical relevance and may lead the development of novel, more specific drugs targeting the 26S proteasome. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologynatural sciencesbiological sciencesmolecular biologystructural biology Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-2013-CIG Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-CIG - Support for training and career development of researcher (CIG) Koordynator MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Wkład UE € 75 000,00 Adres HOFGARTENSTRASSE 8 80539 Munchen Niemcy Zobacz na mapie Region Bayern Oberbayern München, Kreisfreie Stadt Rodzaj działalności Research Organisations Kontakt administracyjny Anne Katrin Werenskiold (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych