A spectroscopic study of uranyl-cytochrome b5/cytochrome c interactions.
Abstract: Uranium is harmful to human health due to its radiation damage and the ability of uranyl ion (UO2(2+)) to interact with various proteins and disturb their biological functions. Cytochrome b5 (cyt b5) is a highly negatively charged heme protein and plays a key role in mediating cytochrome c (cyt c) signaling in apoptosis by forming a dynamic cyt b5-cyt c complex. In previous molecular modeling study in combination with UV-Vis studies, we found that UO2(2+) is capable of binding to cyt b5 at surface residues, Glu37 and Glu43. In this study, we further investigated the structural consequences of cyt b5 and cyt c, as well as cyt b5-cyt c complex, upon uranyl binding, by fluorescence spectroscopic and circular dichroism techniques. Moreover, we proposed a uranyl binding site for cyt c at surface residues, Glu66 and Glu69, by performing a molecular modeling study. It was shown that uranyl binds to cyt b5 (KD=10 μM), cyt c (KD=87 μM), and cyt b5-cyt c complex (KD=30 μM) with a different affinity, which slightly alters the protein conformation and disturbs the interaction of cyt b5-cyt c complex. Additionally, we investigated the functional consequences of uranyl binding to the protein surface, which decreases the inherent peroxidase activity of cyt c. The information of uranyl-cyt b5/cyt c interactions gained in this study likely provides a clue for the mechanism of uranyl toxicity.
Copyright © 2013 Elsevier B.V. All rights reserved.
Publication Date: 2013-09-03 PubMed ID: 24051281DOI: 10.1016/j.saa.2013.08.112Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research explores how uranium, in the form of uranyl ion, affects certain key proteins (cyt b5 and cyt c) in the body thereby contributing to uranium toxicity.
Research Objectives
- This project aimed to understand the impact of uranyl ions (UO2(2+)) – a form of uranium – on the functions of cytochrome b5 (cyt b5) and cytochrome c (cyt c), which are crucial proteins involved in biological functions such as signalling in apoptosis (programmed cell death).
- Specifically, the researchers investigated changes in the structure and function of these proteins upon binding with uranyl ions.
Research Methods
- The researchers used fluorescence spectroscopic techniques and circular dichroism techniques, which are methods used for analysing changes in the molecular structure of proteins.
- They also undertook a molecular modelling study to propose a uranyl binding site within the cytochrome c protein.
Key Findings
- The results revealed that the uranyl ion binds to both cyt b5 and cyt c causing slight alterations in their conformation (shape), hence disturbing the interaction between these two proteins. Moreover, the binding of uranyl to the proteins interferes with the cyt b5-cyt c complex (a functional unit of the two proteins working together).
- Uranyl ions bind with different proteins with varying affinity. Its highest affinity was found with cytochrome b5 (KD=10 μM), then with the cytochrome b5-cytochrome c complex (KD=30 μM), and lastly with cytochrome c (KD=87 μM).
- The functional change due to uranyl binding to the protein surface was found to decrease the inherent peroxidase activity of cyt c. The peroxidase activity of a protein reflects its ability to catalyze certain biochemical reactions, hence this decrease represents a negative impact on the protein’s normal functions.
Impact of Findings
- These findings contribute to a better understanding of the mechanisms behind uranyl toxicity, specifically its ability to interfere with important proteins and disturb their functions. This might help in developing strategies to counteract uranium poisoning in the future.
Cite This Article
APA
Sun MH, Liu SQ, Du KJ, Nie CM, Lin YW.
(2013).
A spectroscopic study of uranyl-cytochrome b5/cytochrome c interactions.
Spectrochim Acta A Mol Biomol Spectrosc, 118, 130-137.
https://doi.org/10.1016/j.saa.2013.08.112 Publication
Researcher Affiliations
- School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China.
MeSH Terms
- Animals
- Cattle
- Cytochromes b5 / chemistry
- Cytochromes b5 / metabolism
- Cytochromes c / chemistry
- Cytochromes c / metabolism
- Horses
- Humans
- Ions
- Kinetics
- Models, Molecular
- Peroxidase / metabolism
- Protein Binding
- Spectrometry, Fluorescence
- Uranium / chemistry
- Uranium / metabolism
Citations
This article has been cited 6 times.- Bulavko ES, Pak MA, Ivankov DN. In Silico Simulations Reveal Molecular Mechanism of Uranyl Ion Toxicity towards DNA-Binding Domain of PARP-1 Protein.. Biomolecules 2023 Aug 20;13(8).
- Tong XY, Yang XZ, Gao SQ, Wang XJ, Wen GB, Lin YW. Regulating Effect of Cytochrome b(5) Overexpression on Human Breast Cancer Cells.. Molecules 2022 Jul 17;27(14).
- Guéguen Y, Frerejacques M. Review of Knowledge of Uranium-Induced Kidney Toxicity for the Development of an Adverse Outcome Pathway to Renal Impairment.. Int J Mol Sci 2022 Apr 15;23(8).
- Lin YW. Uranyl Binding to Proteins and Structural-Functional Impacts.. Biomolecules 2020 Mar 16;10(3).
- Jones DL, Andrews MB, Swinburne AN, Botchway SW, Ward AD, Lloyd JR, Natrajan LS. Fluorescence spectroscopy and microscopy as tools for monitoring redox transformations of uranium in biological systems.. Chem Sci 2015 Sep 1;6(9):5133-5138.
- Liu F, Du KJ, Fang Z, You Y, Wen GB, Lin YW. Chemical and biological insights into uranium-induced apoptosis of rat hepatic cell line.. Radiat Environ Biophys 2015 May;54(2):207-16.
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