Structure Determination of FeoB by Electron Crystallography

Iron is an essential nutrient required by virtually all organisms to sustain life at the cellular level. Nevertheless, an excess of cellular iron is toxic due to its participation in uncontrolled redox reactions that generate highly reactive radicals. Therefore, cells need to tightly regulate primary iron uptake and homeostasis. Genetic approaches have identified a number of iron uptake systems in all three kingdoms of life. However, little is known about the structure of primary iron transporters, especially those that participate in the acquisition of ferrous iron (Fell). The goal of this proposal is to determine the structure of the bacterial transporter for Fe(II), FeoB, by electron cystallography, and to understand the function of a highly conserved GTPase domain located that the N-terminus of FeoB. The presence of a GTPase domain is unique among transporter proteins. Yet, the high degree of conservation of the GTPase domain in FeoB-like proteins from other bacteria, including important human pathogens, indicate that some aspect of ferrous iron transport critically depends on GTP binding and/or hydrolysis. An understanding of the detailed mechanism of Fe(II)-transport in bacteria may be exploited for the development of new strategies in the treatment of microbial he development of new strategies in the treatment of microbial infections.