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Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)

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Title Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)
 
Creator BHUKYA, H
BHUJBALRAO, R
BITRA, A
ANAND, R
 
Subject A-FACTOR RECEPTOR
GAMMA-BUTYROLACTONE RECEPTORS
COOPERATIVE DNA-BINDING
STREPTOMYCES-COELICOLOR
TETRACYCLINE RESISTANCE
CRYSTAL-STRUCTURE
ANTIBIOTIC PRODUCTION
MYCOBACTERIUM-SMEGMATIS
SECONDARY METABOLISM
TYLOSIN PRODUCTION
 
Description Antibiotic production and resistance pathways in Streptomyces are dictated by the interplay of transcriptional regulatory proteins that trigger downstream responses via binding to small diffusible molecules. To decipher the mode of DNA binding and the associated allosteric mechanism in the subclass of transcription factors that are induced by gamma-butyrolactones, we present the crystal structure of CprB in complex with the consensus DNA element to a resolution of 3.25 angstrom. 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. The crystal structure revealed that, CprB is bound to DNA as a dimer of dimers with the mode of binding being analogous to the broad spectrum multidrug transporter protein QacR from the antibiotic resistant strain Staphylococcus aureus. It was demonstrated that the CprB displays a cooperative mode of DNA binding, following a clamp and click model. 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 gamma-butyrolactone synthesis and antibiotic regulation pathways in S. coelicolor A3(2).
 
Publisher OXFORD UNIV PRESS
 
Date 2014-12-28T11:34:57Z
2014-12-28T11:34:57Z
2014
 
Type Article
 
Identifier NUCLEIC ACIDS RESEARCH, 42(15)10122-10133
0305-1048
1362-4962
http://dx.doi.org/10.1093/nar/gku587
http://dspace.library.iitb.ac.in/jspui/handle/100/16372
 
Language English