Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Investigating the calcium modulated transport activity by the ferroportin transporter family (#186)

Chandrika Deshpande 1 2 , Reiya Taniguchi 3 , Vicky Xin 1 , Josep Font 4 , Osamu Nureki 3 , Bryan Mackenzie 5 , Mika Jormakka 1 2
  1. The Centenary Institute, Camperdown, NSW, Australia
  2. Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  3. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan
  4. Discipline of Pharmacology, University of Sydney, Sydney, NSW, Australia
  5. Department of Molecular and Cellular Physiology, University of Cincinnati, Ohio, USA

Iron is essential for almost all living organisms owing to its involvement in a number of metabolic and catalytic processes. To date, Ferroportin (FPN) is the only known mammalian iron exporter and is responsible for transportation and distribution of intestinally absorbed iron into plasma. We have recently identified the prokaryotic protein BbFPN from the bacterium Bdellovibrio bacteriovorus, showing 24% sequence identity and 40% similarity with human FPN. We determined the three dimensional structure of BbFPN in two distinct states (outward-facing and inward-facing conformations) providing crucial insights into the structure and function of the FPN transporter family (1).

 More recently, we have determined the structure of a calcium-bound BbFPN at 3.3 Å. The structure is in an inward-facing conformation, with the Ca2+ ion bound in the N-terminal lobe. We are currently using Isothermal titration calorimetry and mutagenesis to characterise the Ca2+ binding to BbFPN, concurrently with measuring Ca2+ dependence of mammalian FPN by transport assays in oocytes. The results will be presented and discussed.

  1. 1) Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin. Reiya Taniguchi, Hideaki E. Kato, Josep Font, Chandrika N. Deshpande, Miki Wada, Koichi Ito, Ryuichiro Ishitani, Mika Jormakka & Osamu Nureki. Nature Communications. 2015.