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Atypical Response Regulator ChxR from Chlamydia trachomatis Is Structurally Poised for DNA Binding
Barta, Michael L. Hickey, John M. Anbanandam, Asokan Dyer, Kevin Hammel, Michal Hefty, P. Scott
Barta, Michael L.
Hickey, John M.
Anbanandam, Asokan
Dyer, Kevin
Hammel, Michal
Hefty, P. Scott
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Abstract
ChxR is an atypical two-component signal transduction response regulator (RR) of the OmpR/PhoB subfamily encoded by the obligate intracellular bacterial pathogen Chlamydia trachomatis. Despite structural homology within both receiver and effector domains to prototypical subfamily members, ChxR does not require phosphorylation for dimer formation, DNA binding or transcriptional activation. Thus, we hypothesized that ChxR is in a conformation optimal for DNA binding with limited interdomain interactions. To address this hypothesis, the NMR solution structure of the ChxR effector domain was determined and used in combination with the previously reported ChxR receiver domain structure to generate a full-length dimer model based upon SAXS analysis. Small-angle scattering of ChxR supported a dimer with minimal interdomain interactions and effector domains in a conformation that appears to require only subtle reorientation for optimal major/minor groove DNA interactions. SAXS modeling also supported that the effector domains were in a head-to-tail
conformation, consistent with ChxR recognizing tandem DNA repeats. The effector domain structure was leveraged to identify key residues that were critical for maintaining protein - nucleic acid interactions. In combination with prior analysis of the essential location of specific nucleotides for ChxR recognition of DNA, a model of the full-length ChxR dimer bound to its cognate cis-acting element was generated.
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Date
2014-03-19
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Public Library of Science
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Keywords
DNA sequences, DNA structure, DNA-binding proteins, Nuclear magnetic resonance, Phosphorylation, Protein structure, Sequence alignment, Small-angle scattering
Citation
Barta ML, Hickey JM, Anbanandam A, Dyer K, Hammel M, et al. (2014) Atypical Response Regulator ChxR from Chlamydia trachomatis Is Structurally Poised for DNA Binding. PLoS ONE 9(3): e91760. http://dx.doi.org/10.1371/journal.pone.0091760