Understanding the role of BAR and SH3 domain-containing proteins in fungi

This thesis addresses the role of SH3 and BAR domain-containing proteins in different fungal species. SH3 domains are small modules that mediate protein-protein interactions and BAR domains are dimerization domains with membrane binding and bending properties. It is known that the ScRvs167 protein interacts via its SH3 domain with other components of the yeast endocytic machinery while its BAR domain dimerizes with the BAR domain of ScRvs161 and as a heterodimer complex is responsible for the membrane deformation that is crucial to vesicle formation as well as release of the vesicle from the plasma membrane in S. cerevisiae. In Chapter 2, we characterize a novel N-BAR heterodimer in C. albicans that consists of the Rvs162 and Rvs167-3 proteins and we show that in contrast to Rvs161/Rvs167 heterodimer it does not have an endocytic role. In Chapter 3 we demonstrate fission yeast proteins Hob1 and Hob3 (homologs of S. cerevisiae Rvs167 and Rvs161, respectively) ability to form heterodimers in vitro even though evidence suggests they have different functions. Sfp47, a novel F-BAR protein in S. pombe is the focus of Chapter 4. In the last two chapters we are focusing on SH3 domains and their interaction with peptide ligands. In Chapter 5 we investigate the evolution of SH3 domain-mediated interactions in fungi. In Chapter 6 we investigate the CaRvs167-3 SH3 domain: peptide ligand interaction. We conclude that CaRvs167-3 SH3 domain can bind to a peptide completely devoid of proline residues and we establish a novel binding sequence for the Rvs167-3 SH3.