Structural Insights Into the Effects of Interactions With Iron and Copper Ions on Ferritin From the Blood Clam Tegillarca granosa

Tinghong Ming; Qinqin Jiang; Chunheng Huo; Hengshang Huan; Yan Wu; Chang Su; Xiaoting Qiu; Chenyang Lu; Jun Zhou; Ye Li; Jiaojiao Han; Zhen Zhang; Xiurong Su

doi:10.3389/fmolb.2022.800008

Structural Insights Into the Effects of Interactions With Iron and Copper Ions on Ferritin From the Blood Clam Tegillarca granosa

Front Mol Biosci. 2022 Mar 11:9:800008. doi: 10.3389/fmolb.2022.800008. eCollection 2022.

Authors

Tinghong Ming^{1

2}, Qinqin Jiang^{1

3}, Chunheng Huo^{1

2}, Hengshang Huan^{1

3}, Yan Wu^{1

3}, Chang Su⁴, Xiaoting Qiu³, Chenyang Lu^{1

2}, Jun Zhou^{1

2}, Ye Li^{1

2}, Jiaojiao Han^{1

2}, Zhen Zhang^{1

2}, Xiurong Su^{1

2}

Affiliations

¹ State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China.
² School of Marine Science, Ningbo University, Ningbo, China.
³ College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China.
⁴ Zhejiang Collaborative Innovation Center for High Value Utilization of Byproducts from Ethylene Project, Ningbo Polytechnic College, Ningbo, China.

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.

Keywords: Cu2+ ion; Fe2+ ion; blood clam Tegillarca granosa; catalytic activity; crystal structure; ferritin.