Exploring the structure function relationship of membrane-pore-forming FGF2 oligomers - a single molecule approach

Fibroblast Growth Factor 2 (FGF2) is a cell survival factor mediating tumor-induced angiogenesis. As opposed to the majority of extracellularly localized proteins, FGF2 is secreted from cells by direct protein translocation across the plasma membrane. Several lines of evidence suggest membrane-inserted FGF2 oligomers to represent key intermediates of this process forming lipidic membrane pores. In this project, we build upon our previous work and are aiming at the determination of the precise oligomeric state of FGF2 intermediates, the analysis of a potential role of a protein ATP1A1 in initiating oligomerization of FGF2 and studying the role of heparan sulfates in facilitating the formation of FGF2 translocation intermediates. We will use state-of-the art single molecule techniques and expect to gain insight into the molecular mechanism of FGF2 membrane translocation at an unprecedented level of detail. Therefore, our studies will make a significant contribution to our understanding of the molecular mechanism by which tumor cells secrete FGF2