Ming Tinghong, Jiang Qinqin, Huo Chunheng, Huan Hengshang, Wu Yan, Su Chang, Qiu Xiaoting, Lu Chenyang, Zhou Jun, Li Ye, Han Jiaojiao, Zhang Zhen, Su Xiurong
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China.
School of Marine Science, Ningbo University, Ningbo, China.
Front Mol Biosci. 2022 Mar 11;9:800008. doi: 10.3389/fmolb.2022.800008. eCollection 2022.
In addition to its role as an iron storage protein, ferritin can function as a major detoxification component in the innate immune defense, and Cu ions can also play crucial antibacterial roles in the blood clam, . However, the mechanism of interaction between iron and copper in recombinant ferritin (TgFer) remains to be investigated. In this study, we investigated the crystal structure of TgFer and examined the effects of Fe and Cu 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. Cu ions appear to bind preferentially with the 3-fold channel as well as ferroxidase site over Fe 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 Fe and Cu ions.
除了作为一种铁储存蛋白发挥作用外，铁蛋白还可作为天然免疫防御中的主要解毒成分发挥作用，并且铜离子在血蚶中也可发挥关键的抗菌作用。然而，重组铁蛋白（TgFer）中铁与铜之间的相互作用机制仍有待研究。在本研究中，我们研究了TgFer的晶体结构，并考察了铁离子和铜离子对TgFer结构及催化活性的影响。晶体结构显示，TgFer在由24个相同亚基组成的笼状球形外壳中呈现出典型的4-3-2对称性，在铁氧化酶中心和3倍通道中均具有高度保守的结构。结构和生化分析表明，TgFer的4倍通道可作为金属离子的潜在结合位点。铜离子似乎比铁离子更优先地与3倍通道以及铁氧化酶位点结合，这可能会抑制TgFer的铁氧化酶活性。我们的结果展示了TgFer的结构和功能特征，为深入了解TgFer与铁离子和铜离子之间的相互作用机制提供了依据。
