Abstract
In addition to its role as an iron storage protein, ferritin can function as a major detoxification component in the innate immune defense, and Cu2+ ions can also play crucial antibacterial roles in the blood clam, Tegillarca granosa. However, the mechanism of interaction between iron and copper in recombinant Tegillarca granosa ferritin (TgFer) remains to be investigated. In this study, we investigated the crystal structure of TgFer and examined the effects of Fe2+ and Cu2+ ions on the TgFer structure and catalytic activity. The crystal structure revealed that TgFer presented a typically 4–3–2 symmetry in a cage-like, spherical shell composed of 24 identical subunits, featuring highly conserved organization in both the ferroxidase center and the 3-fold channel. Structural and biochemical analyses indicated that the 4-fold channel of TgFer could be serviced as potential binding sites of metal ions. Cu2+ ions appear to bind preferentially with the 3-fold channel as well as ferroxidase site over Fe2+ ions, possibly inhibiting the ferroxidase activity of TgFer. Our results present a structural and functional characterization of TgFer, providing mechanistic insight into the interactions between TgFer and both Fe2+ and Cu2+ ions.
Highlights
Ferritin represents a ubiquitous class of nanocage-like proteins that are primarily involved in maintaining iron homeostasis (Bou-Abdallah et al, 2018)
After purification using a nickel-nitrilotriacetic acid (Ni-NTA) affinity column, the protein was further purified by gel filtration prior to crystallization, the sample was analyzed using a gelfiltration chromatography column, resulting in a peak at approx. 15 ml, which is consistent with the Tegillarca granosa ferritin (TgFer) 24-mer (Figure 1C)
This study was performed to determine the crystal structural characteristics of TgFer, TgFer + Cu, TgFer + Fe, and TgFer + CuFe at resolutions of 1.78, 2.30, 1.85, and 3.90 Å, respectively. These structures exhibited a typically cage-like spherical shell composed of 24 identical subunits, in which the highly conserved organization of both the ferroxidase center and the 3-fold channel suggested the common function of directing iron into the cavity for Fe2+ ion oxidation
Summary
Ferritin represents a ubiquitous class of nanocage-like proteins that are primarily involved in maintaining iron homeostasis (Bou-Abdallah et al, 2018). Ferritin is known to be an essential protein that plays dual roles in iron storage and detoxification in almost all living systems (Plays et al, 2021). Ferritin plays a central role in taking up iron (as Fe2+) and storing it in a stable and unreactive form (as Fe3+-oxide/ hydroxide) (Theil, 2012). Estimations suggest that up to 4,000 iron atoms can be stored inside the inner cavity of a single ferritin molecule (Plays et al, 2021). Despite significant differences in the primary sequences of different ferritin proteins, the tertiary and quaternary structures of known ferritins have been demonstrated to be strikingly similar
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
