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Science 16 July 2004:
Vol. 305. no. 5682, pp. 386 - 389
DOI: 10.1126/science.1097064
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Reports

Structure and Flexibility Adaptation in Nonspecific and Specific Protein-DNA Complexes

Charalampos G. Kalodimos,1* Nikolaos Biris,1* Alexandre M. J. J. Bonvin,1 Marc M. Levandoski,2 Marc Guennuegues,1 Rolf Boelens,1 Robert Kaptein1{dagger}

Interaction of regulatory DNA binding proteins with their target sites is usually preceded by binding to nonspecific DNA. This speeds up the search for the target site by several orders of magnitude. We report the solution structure and dynamics of the complex of a dimeric lac repressor DNA binding domain with nonspecific DNA. The same set of residues can switch roles from a purely electrostatic interaction with the DNA backbone in the nonspecific complex to a highly specific binding mode with the base pairs of the cognate operator sequence. The protein-DNA interface of the nonspecific complex is flexible on biologically relevant time scales that may assist in the rapid and efficient finding of the target site.

1 Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.
2 Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.



* Present address: Department of Chemistry, Rutgers University, Newark, NJ 07102, USA.

{dagger} To whom correspondence should be addressed. E-mail: kaptein{at}nmr.chem.uu.nl

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