کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2188370 1096164 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Role of High Affinity Non-specific DNA Binding by Lrp in Transcriptional Regulation and DNA Organization
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
The Role of High Affinity Non-specific DNA Binding by Lrp in Transcriptional Regulation and DNA Organization
چکیده انگلیسی

Transcriptional regulatory proteins typically bind specific DNA sequences with ∼103–107-fold higher affinity than non-specific DNA and this discrimination is essential for their in vivo function. Here we show that the bacterial leucine-responsive regulatory protein (Lrp) does not follow this trend and has a ∼20–400-fold binding discrimination between specific and non-specific DNA sequences. We suggest that the dual function of Lrp to regulate genes and to organize DNA utilizes this unique property. A ∼20-fold decrease in binding affinity from specific DNA is dependent upon cryptic binding sites, including the sequence GN2-3TTT and A-tracts. Removal of these sites still results in high binding affinity, only ∼70-fold weaker than that of specific sites. Similar to Lrp's binding of specific sites in the pap and ilvIH promoters, Lrp binds cooperatively to non-specific DNA; thus, protein/protein interactions are important for both specific and non-specific DNA binding. When considering this cooperativity of Lrp binding, the binding selectivity to specific sites may increase to a maximum of ∼400-fold. Neither leucine nor the pap-specific local regulator PapI alter Lrp's non-specific binding affinity or cooperative binding of non-specific DNA. We hypothesize that Lrp combines low sequence discrimination and relatively high intracellular protein concentrations to ensure its ability to regulate the transcription of specific genes while also functioning as a nucleoid-associated protein. Modeling of Lrp binding data and comparison to other proteins with regulatory and nucleoid-associated properties suggests similar mechanisms.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 369, Issue 5, 22 June 2007, Pages 1307–1317
نویسندگان
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