CCeMMP Seminar Series – Dr. Alastair Stewart – May 2024

In this seminar Alastair will present recent cryo-EM studies on two different membrane proteins:

(i) F1Fo ATP synthase, a biological rotary generator essential for cellular energy, utilises proton flow through its membrane motor to drive rotation and catalyse ATP production in the soluble F 1 motor. Using cryo-EM, rotational sub-states and torsional flexibilities have been revealed, enhancing the understanding of its catalytic mechanism and regulatory domains.

(ii) OCT1 mediates the hepatic uptake of various metabolites and drugs, with genetic variations affecting their efficacy and safety. Using cryo-EM, structures of OCT1 have been solved in outward and inward states, bound to a series of drugs. Combined with functional assays, these structures reveal OCT1’s broad substrate recognition and provide insights into its substrate translocation mechanism, highlighting the role of hydrophobic gates and charge neutralisation on drug binding.

Dr. Alastair Stewart

Victor Chang Cardiac Research Institute,

Sydney