Speaker
Description
Iron is an essential trace element that, when in excess, becomes highly toxic [1]. Intracellular iron concentration must be strictly regulated by a network of interacting mechanisms [2]. Ferritin is a ubiquitous iron-storage protein that forms a highly conserved 24-subunit spherical cage-like structure. Ferritin catalyses the oxidation of iron (II) to iron (III) and sequesters the newly oxidised iron (III) as a mineral core to prevent cellular damage [3]. In this study, we use the model organism, Caenorhabditis elegans, to investigate iron uptake, oxidation, storage and release by ferritin.
C. elegans expresses two ferritin proteins, FTN-1 and FTN-2, which both exhibit ferroxidase activity [4]. FTN-2 functions at a rate significantly faster than FTN-1 despite conservation of all catalytic residues, suggesting that structural differences at a location distinct to the ferroxidase centre may influence catalytic activity. We solved the X-ray crystal structures of FTN-1 (1.84 Å) and FTN-2 (1.47 Å), and the cryo-EM structure of FTN-2 (1.88 Å). FTN-1 and FTN-2 both adopt the conserved 24-subunit cage-like structure and bind one iron (II) in the ferroxidase centre of each chain. We postulate that iron (II) accesses the ferroxidase centre through a three-fold symmetrical pore. This pore is notably larger and more negatively charged in the FTN-2 structure and may facilitate easier access of iron (II) to the ferroxidase centre, resulting in a faster catalysis rate.
These structural insights further our understanding of the mechanisms used by ferritin to regulate iron storage and the overall role of ferritin in iron homeostasis.
| Which facility did you use for your research | Australian Synchrotron |
|---|---|
| Condition of submission | Yes |
| Pronouns | She/Her |
| Presenter Gender | Woman |
| Level of Expertise | Early Career <5 Years |
