A quantitative understanding of lac repressor’s binding specificity and flexibility

Zheng Zuo, Yiming Chang, Gary D. Stormo

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Quant. Biol. ›› 2015, Vol. 3 ›› Issue (2) : 69-80. DOI: 10.1007/s40484-015-0044-z
RESEARCH ARTICLE
RESEARCH ARTICLE

A quantitative understanding of lac repressor’s binding specificity and flexibility

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Abstract

Lac repressor, the first discovered transcriptional regulator, has been shown to confer multiple modes of binding to its operator sites depending on the central spacer length. Other homolog members in the LacI/GalR family (PurR and YcjW) cannot bind their operator sites with similar structural flexibility. To decipher the underlying mechanism for this unique property, we used Spec-seq approach combined with site-directed mutagenesis to quantify the DNA binding specificity of multiple hybrids of lacI and PurR. We find that lac repressor’s recognition di-residues YQ and its hinge helix loop regions are both critical for its structural flexibility. Also, specificity profiling of the whole lac operator suggests that a simple additive model from single variants suffice to predict other multivariant sites’ energy reasonably well, and the genome occupancy model based on this specificity data correlates well with in vivo lac repressor binding profile.

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Keywords

lac repressor / binding flexibility / Spec-seq / ionic strength

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Zheng Zuo, Yiming Chang, Gary D. Stormo. A quantitative understanding of lac repressor’s binding specificity and flexibility. Quant. Biol., 2015, 3(2): 69‒80 https://doi.org/10.1007/s40484-015-0044-z
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SUPPLEMENTARY MATERIALS

The supplementary materials can be found online with this article at DOI 10.1007/s40484-015-0044-z.
We thank members of the Stormo Lab for useful comments on the work. We thank the anonymous reviewers in our previous paper[4] who provided helpful insights on lacI’s structural property. Funding for this work was from NIH grants HG000249 and HG005970.
Zheng Zuo, Yiming Chang, and Gary D. Stormo declare they have no conflict of interest, conform with the Helsinki Declaration of 1975, as revised in 2000 (5) concerning Human and animal Rights, and follow out policy concerning Informed Consent as shown on Springer.com.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
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