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Weak operator binding enhances simulated lac repressor‐mediated DNA looping
Author(s) -
Colasanti Andrew V.,
Grosner Michael A.,
Perez Pamela J.,
Clauvelin Nicolas,
Lu XiangJun,
Olson Wilma K.
Publication year - 2013
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22336
Subject(s) - lac repressor , repressor , lac operon , dna , operator (biology) , chemistry , computational biology , biophysics , operon , genetics , biology , escherichia coli , gene , biochemistry , gene expression , plasmid
The 50th anniversary of Biopolymers coincides closely with the like celebration of the discovery of the Escherichia coli (lac) lactose operon, a classic genetic system long used to illustrate the influence of biomolecular structure on function. The looping of DNA induced by the binding of the Lac repressor protein to sequentially distant operator sites on DNA continues to serve as a paradigm for understanding long‐range genomic communication. Advances in analyses of DNA structures and in incorporation of proteins in computer simulations of DNA looping allow us to address long‐standing questions about the role of protein‐mediated DNA loop formation in transcriptional control. Here we report insights gained from studies of the sequence‐dependent contributions of the natural lac operators to Lac repressor‐mediated DNA looping. Novel superposition of the ensembles of protein‐bound operator structures derived from NMR measurements reveals variations in DNA folding missed in conventional structural alignments. The changes in folding affect the predicted ease with which the repressor induces loop formation and the ways that DNA closes between the protein headpieces. The peeling of the auxiliary operators away from the repressor enhances the formation of loops with the 92‐bp wildtype spacing and hints of a structural reason behind their weak binding. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 1070–1081, 2013.

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