Article Dans Une Revue Biophysical Journal Année : 2019

Modifying Zinc Fingers: Targeting the Inflammatory Zinc Finger Protein, Tristetraprolin, with Exogenous Gold Complexes and Determining a Role for H2S in Modifying Trisetrapolin Endogenously

Résumé

Tristetraprolin (TTP) is a non-classical Zinc Finger protein (ZF), that contains two Cys3His zinc binding domains, and which regulates the inflammatory response at the mRNA level. TTP is a potential target for exogenous anti-inflammatory gold complexes and the endogenous signaling molecule, H2S. To understand how TTP is targeted by gold complexes, the interactions between the model gold complex, [Au(III)(terpy)Cl]Cl2 (Auterpy) and TTP were investigated using a combination of optical spectroscopy and native electrospray ionization mass spectrometry (ESI-MS) as well as X-ray absorption study (XAS). We discovered that gold exchanges with zinc bound to TTP forming a series of Aux-TTP-2D complexes, with reduction of the gold from Au3+ to Au1+. These protein is then functionally inactive (no RNA binding). When the same experiments were performed with TTP bound to RNA, the Zn-TTP/RNA complex is not disrupted by Auterpy providing potential evidence possible mechanism for its anti-inflammatory properties. To understand how H2S, a naturally occurring signaling molecule, targets Zn-TTP, its reactivity was determined using a combination of cryo-ESI-MS, fluorescence and electron paramagnetic resonance (EPR) spectroscopies. We discovered the H2S oxidizes the cysteine residues of Zn-TTP via a mechanism that involves atmospheric oxygen, a persulfide intermediate and a radical reaction. The results of both studies will be presented in the context of TTP's biological role.

Dates et versions

hal-04833280 , version 1 (12-12-2024)

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Kiwon Ok, Wenjing Li, Geoffrey D. Shimberg, Sharon Batelu, Mike Lange, et al.. Modifying Zinc Fingers: Targeting the Inflammatory Zinc Finger Protein, Tristetraprolin, with Exogenous Gold Complexes and Determining a Role for H2S in Modifying Trisetrapolin Endogenously. Biophysical Journal, 2019, 116 (3), pp.480a. ⟨10.1016/j.bpj.2018.11.2591⟩. ⟨hal-04833280⟩
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