Revealing the DNA Binding Modes of CsoR by EPR Spectroscopy

Yasmin Igbaria-Jaber, Lukas Hofmann, Lada Gevorkyan-Airapetov, Yulia Shenberger, Sharon Ruthstein

Research output: Contribution to journalArticlepeer-review


In pathogens, a unique class of metalloregulator proteins, called gene regulatory proteins, sense specific metal ions that initiate gene transcription of proteins that export metal ions from the cell, thereby preventing toxicity and cell death. CsoR is a metalloregulator protein found in various bacterial systems that “sense” Cu(I) ions with high affinity. Upon copper binding, CsoR dissociates from the DNA promoter region, resulting in initiation of gene transcription. Crystal structures of CsoR in the presence and absence of Cu(I) from various bacterial systems have been reported, suggesting either a dimeric or tetrameric structure of these helical proteins. However, structural information about the CsoR-DNA complex is missing. Here, we applied electron paramagnetic resonance (EPR) spectroscopy to follow the conformational and dynamical changes that Mycobacterium tuberculosis CsoR undergoes upon DNA binding in solution. We showed that the quaternary structure is predominantly dimeric in solution, and only minor conformational and dynamical changes occur in the DNA bound state. Also, labeling of the unresolved C- terminus revealed no significant change in dynamics upon DNA binding. These observations are unique, since for other bacterial copper metalloregulators, such as the MerR and CopY families, major conformational changes were observed upon DNA binding, indicating a different mode of action for this protein family.

Original languageEnglish
Pages (from-to)39886-39895
Number of pages10
JournalACS Omega
Issue number42
StatePublished - 24 Oct 2023

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© 2023 The Authors. Published by American Chemical Society.


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