Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2).
Bottom Line: Binding of the DNA results in the restructuring of the dimeric interface of CprB, inducing a pendulum-like motion of the helix-turn-helix motif that inserts into the major groove.Experiments performed on a subset of DNA sequences from Streptomyces coelicolor A3(2) suggest that CprB is most likely a pleiotropic regulator.Apart from serving as an autoregulator, it is potentially a part of a network of proteins that modulates the γ-butyrolactone synthesis and antibiotic regulation pathways in S. coelicolor A3(2).
Affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, Maharashtra, India IITB-Monash Research Academy, Mumbai 400076, Maharashtra, India.Show MeSH
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Mentions: Within the dimer of dimers sub-class, even though the mode of binding is similar, an analysis of the structures shows that the angles between the two homodimers with respect to the DNA differs (Figure 7). The angle between the homodimers of CprB and DNA is found to be 142°. For the QacR–DNA (Figure 7A), CgmR–DNA (Figure 7B) and SlmA–DNA complexes (Figure 7C), it is 130°, 145° (30) and 130°, respectively. In the case of MS6564–DNA complex, this bend is not present and the angle is around 180° corresponding to a conformation closer to the ideal B-form (shown in Figure 7D). It appears that the angle between the homodimers is an alternative representation of the distortion introduced into the DNA upon protein binding and can be broadly correlated to the specificity of DNA recognition. For instance, CgmR, QacR, SlmA and CprB that introduce distortion in the DNA, are sequence-specific regulators. They identify their cognate DNA sequences by an induced-fit mechanism through widening of the groove to enable requisite protein–DNA contacts. In contrast, MS6564, a global regulator does not induce a deformation in the DNA structure and interacts with the DNA through a network of water molecules, ensuring proper scanning over a long stretch of generic sequences (33).
Affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, Maharashtra, India IITB-Monash Research Academy, Mumbai 400076, Maharashtra, India.