Conformational change induced by binding of Mn2+ ions activates SloR transcription factor in Streptococcus mutans.

IF 7.7 1区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Katarina Radman, Ivo Crnolatac, Nikola Bregović, Zoe Jelić Matošević, Pedro A Fernandes, Dalibor Merunka, Dijana Žilić, Ivo Piantanida, Ivana Leščić Ašler, Branimir Bertoša
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引用次数: 0

Abstract

Streptococcus mutans, a bacterium commonly found in the human oral cavity, is considered the primary causative agent of dental caries. A key player in the pathophysiology of S. mutans is SloR, a 25-kDa metalloregulatory protein. SloR plays a crucial role in coordinating the uptake of essential metal ions, particularly manganese, with the transcription of the bacterium's virulence genes. To elucidate the molecular mechanism underlying the enhanced binding affinity of SloR to DNA upon Mn2+ ion binding, a combination of computational (QM and MD) and experimental (ITC, DSC, CD, EPR) methods have been employed. Computational simulations revealed that Mn2+ binding induces a conformational change of SloR, primarily affecting the positioning of its DNA-binding domains, bringing them to an appropriate position for DNA binding. Consequently, the protein's DNA binding affinity is modulated. Additionally, experimental findings indicate that the SloR monomer binds up to three Mn2+ ions and that the thermodynamic stability of SloR increases upon Mn2+ complexation. The presented computational results also suggest that Mn2+ binding at the primary binding sites is sufficient to trigger the observed conformational change in SloR.

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来源期刊
International Journal of Biological Macromolecules
International Journal of Biological Macromolecules 生物-生化与分子生物学
CiteScore
13.70
自引率
9.80%
发文量
2728
审稿时长
64 days
期刊介绍: The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.
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