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Interplay of Protein and DNA Structure Revealed in Simulations of the lac Operon

Czapla, L and Grosner, MA and Swigon, D and Olson, WK (2013) Interplay of Protein and DNA Structure Revealed in Simulations of the lac Operon. PLoS ONE, 8 (2).

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The E. coli Lac repressor is the classic textbook example of a protein that attaches to widely spaced sites along a genome and forces the intervening DNA into a loop. The short loops implicated in the regulation of the lac operon suggest the involvement of factors other than DNA and repressor in gene control. The molecular simulations presented here examine two likely structural contributions to the in-vivo looping of bacterial DNA: the distortions of the double helix introduced upon association of the highly abundant, nonspecific nucleoid protein HU and the large-scale deformations of the repressor detected in low-resolution experiments. The computations take account of the three-dimensional arrangements of nucleotides and amino acids found in crystal structures of DNA with the two proteins, the natural rest state and deformational properties of protein-free DNA, and the constraints on looping imposed by the conformation of the repressor and the orientation of bound DNA. The predicted looping propensities capture the complex, chain-length-dependent variation in repression efficacy extracted from gene expression studies and in vitro experiments and reveal unexpected chain-length-dependent variations in the uptake of HU, the deformation of repressor, and the folding of DNA. Both the opening of repressor and the presence of HU, at levels approximating those found in vivo, enhance the probability of loop formation. HU affects the global organization of the repressor and the opening of repressor influences the levels of HU binding to DNA. The length of the loop determines whether the DNA adopts antiparallel or parallel orientations on the repressor, whether the repressor is opened or closed, and how many HU molecules bind to the loop. The collective behavior of proteins and DNA is greater than the sum of the parts and hints of ways in which multiple proteins may coordinate the packaging and processing of genetic information. © 2013 Czapla et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Czapla, L
Grosner, MA
Swigon, Dswigon@pitt.eduSWIGON
Olson, WK
Date: 14 February 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0056548
Schools and Programs: Dietrich School of Arts and Sciences > Mathematics
Refereed: Yes
Other ID: NLM PMC3572996
PubMed Central ID: PMC3572996
PubMed ID: 23457581
Date Deposited: 28 Mar 2013 16:43
Last Modified: 02 Feb 2019 15:59


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