Nadine Smolinski
PhD project
In proliferating cells Asc1p appears bound to the ribosome whereas in quiescent stationary phase cultures increasing amounts of free cytosolic Asc1p emerges. It physically interacts with a multitude of other proteins, as e.g. the c-subunit of elongation factor 3, eIF3c/Nip1, and by that might affect the process of mRNA translation at ribosomes. Asc1p phosphorylation might influence protein-protein interactions. We will verify known Asc1p interaction partners and analyze in depth the structural properties underlying the protein-protein interactions by the application of cross-link chemistry and high-resolution mass spectrometry (MS3D). By the use of different cross-linking strategies with either bifunctional cross-linkers (e.g. BS2G, in vitro) or incorporated UV-activated cross-linkers (e.g. Bpa, in vitro, in vivo) purified components will be analyzed for their sites of interactions. The impact and consequences of Asc1p phosphorylation on its interacting capabilities will be studied by the use of mutated ASC1 alleles encoding protein isoforms with amino acid substitutions mimicking either the phosphorylated or the unphosphorylated state at the respective phosphosites. Promising protein-protein interactions are intended to be further analyzed with X-ray crystallography in combination with protein modeling software.
Nadine Smolinski is member of the MassSpec-Yeast group.