Poster Presentation The 47th Lorne Conference on Protein Structure and Function 2022

Towards a structural understanding of drug transport in the SLC22 family (#110)

Yi C Zeng 1 2 , Jamie I Vandenberg 1 2 , Renae M Ryan 3 , Alastair G Stewart 1 2
  1. Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
  2. Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
  3. School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia

The SLC22 family of organic cation and anion transporters mediate the transfer of a range of endogenous and xenobiotic compounds across the cell membrane. These transporters are pivotal in the absorption and excretion of a number of drug compounds, however, a structural understanding of their function and substrate selectivity is lacking. Here, we describe the initial progress towards the purification of one member, human organic cation transporter 1 (OCT1). OCT1 was recombinantly expressed in HEK293 cells and purified, revealing some features of its oligomerisation state. We also discuss strategies for cryo-EM sample preparation and data collection and how our initial model determined from cryo-EM compares to predicted models of OCT1. A high resolution structure of this transporter will help aid the identification of drug-drug interactions in current and future small molecule treatments.