Computer simulations reveal changes in the conformational space of the transcriptional regulator MosR upon the formation of a disulphide bond and in the collective motions that regulate its DNA-binding affinity

PloS One
Amanda Souza Câmara, Eduardo Horjales

Abstract

M. tuberculosis oxidation sense Regulator (MosR) is a transcriptional regulator from Mycobacterium tuberculosis. It senses the environment oxidation and regulates the expression of a secreted oxidoreductase, thus defending the bacilli against oxidative stress from the phagosome. While most of the members of the Multiple antibiotics resistance Regulator (MarR) family are ligand-responsive, MosR may dissociate from its DNA site upon formation of an intrachain disulphide bond. However, the structure of MosR in its oxidized state is not known, and it is not clear how the formation of this disulphide bond would lead to the conformational changes required for dissociation of the DNA. Nonetheless, MosR presents two crystallographically resolved conformations in its reduced state: bound and unbound to DNA. We managed to simulate MosR unbound to the DNA, both in the presence and in the absence of the disulphide bond. Our results indicate that this disulphide bond precludes the N-terminal residues from adopting a conformation that stands in-between the helix α1 and the DNA binding domain (DBD) from the other chain. Once this conformation is achieved in the reduced state, this DBD detaches from the dimerization domain and becomes more fle...Continue Reading

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Citations

Mar 17, 2020·Journal of Biomolecular Structure & Dynamics·Clauber Henrique Souza da CostaJerônimo Lameira

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Methods Mentioned

BETA
electrophoretic mobility shift
NMR

Software Mentioned

Gromacs
MosR
NMA
Coot
VMD
PyMOL

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