Ligand-induced conformational changes and conformational dynamics in the solution structure of the lactose repressor protein

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dc.contributor.authorTaraban, Men_AU
dc.contributor.authorZhan, HLen_AU
dc.contributor.authorWhitten, AEen_AU
dc.contributor.authorLangley, DBen_AU
dc.contributor.authorMatthews, KSen_AU
dc.contributor.authorSwint-Kruse, Len_AU
dc.contributor.authorTrewhella, Jen_AU
dc.date.accessioned2009-06-16T05:26:30Zen_AU
dc.date.accessioned2010-04-30T05:01:36Zen_AU
dc.date.available2009-06-16T05:26:30Zen_AU
dc.date.available2010-04-30T05:01:36Zen_AU
dc.date.issued2008-02-15en_AU
dc.date.statistics2008-02-15en_AU
dc.description.abstractWe present here the results of a series of small-angle X-ray scattering studies aimed at understanding the role of conformational changes and structural flexibility in DNA binding and allosteric signaling in a bacterial transcription regulator, lactose repressor protein (LacI). Experiments were designed to detect possible conformational changes that occur when LacI binds either DNA or the inducer IPTG, or both. Our studies included the native LacI dimer of homodimers and a dimeric variant (R3), enabling us to probe conformational changes within the homodimers and distinguish them from those involving changes in the homodimer-homodimer relationships. The scattering data indicate that removal of operator DNA (oDNA) from R3 results in an unfolding and extension of the hinge helix that connects the LacI regulatory and DNA-binding domains. In contrast, only very subtle conformational changes occur in the R3 dimer-oDNA complex upon IPTG binding, indicative of small adjustments in the orientations of domains and/or subdomains within the structure. The binding of IPTG to native (tetrameric) LacI-oDNA complexes also appears to facilitate a modest change in the average homodimer-homodimer disposition. Notably, the crystal structure of the native LacI-oDNA complex differs significantly from the average solution conformation. The solution scattering data are best fit by an ensemble of structures that includes (1) similar to 60% of the V-shaped dimer of homodimers observed in the crystal structure and (2) similar to 40% of molecules with more "open" forms, such as those generated when the homodimers move with respect to each other about the tetramerization domain: In gene regulation, such a flexible LacI would be beneficial for the interaction of its two DNA-binding domains, positioned at the tips of the V, with the required two of three LacI operators needed for full repression. © 2007, Elsevier Ltd.en_AU
dc.identifier.citationTaraban, M., Zhan, H., Whitten, A. E., Langley, D. B., Matthews, K. S., Swint-Kruse, L., & Trewhella, J. (2008). Ligand-induced conformational changes and conformational dynamics in the solution structure of the lactose repressor protein. Journal of Molecular Biology, 376(2), 466-481. doi:10.1016/j.jmb.2007.11.067en_AU
dc.identifier.govdoc1092en_AU
dc.identifier.issn0022-2836en_AU
dc.identifier.issue2en_AU
dc.identifier.journaltitleJournal of Molecular Biologyen_AU
dc.identifier.pagination466-481en_AU
dc.identifier.urihttp://dx.doi.org/10.1016/j.jmb.2007.11.067en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/1376en_AU
dc.identifier.volume376en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.subjectSmall angle scatteringen_AU
dc.subjectCrystal structureen_AU
dc.subjectLactoseen_AU
dc.subjectProteinsen_AU
dc.subjectDNAen_AU
dc.subjectBinding energyen_AU
dc.titleLigand-induced conformational changes and conformational dynamics in the solution structure of the lactose repressor proteinen_AU
dc.typeJournal Articleen_AU
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