ABC Transporters in H. Influenzae

Abstract

Our research strives to understand how proteins embedded in the cellular membrane allow compounds to enter or exit the cell. Adenosine triphosphate (ATP)-Binding Cassette (ABC) transporters work as membrane bound molecular pumps to transport broad spectrum of substrates, including sugars, peptides or toxins across cellular membranes. Present in all organisms, ABC transporters can be divided into two classes, (i) exporters that mediate expulsion of unrelated substances across cell membranes and (ii) which function to allow nutrients into the cell. In both classes, ABC transporters use the energy source adenosine triphosphate (ATP) to carry out this biological process, which is evolutionarily preserved across all organisms. By combining biochemical experiments with structural biology, we seek to understand how the conversion of ATP to ADP controls the conformational changes of an ABC importer, which in turn allows substrates to enter the cell. Since the current mechanism of membrane transport for importers is incomplete, understanding the transport process requires a comprehensive structural analysis of one full length ABC transporter trapped in different conformations along the transport process. This research program has set out to close critical gaps in the understanding of the fundamentals of the transport mechanism in bacterial pathogens. The results will yield insights into how type II transporters utilize ATP hydrolysis to coordinate transport across all organisms, crucial for cell viability.