Structure and flexibility adaptation in nonspecific and specific protein-DNA complexes.
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.
Kalodimos
Charalampos G
CG
Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.
Biris
Nikolaos
N
Bonvin
Alexandre M J J
AM
Levandoski
Marc M
MM
Guennuegues
Marc
M
Boelens
Rolf
R
Kaptein
Robert
R
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D020029:Base Pairing; D001665:Binding Sites; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D004058:Diffusion; D019281:Dimerization; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D056968:Lac Repressors; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009875:Operator Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D013816:Thermodynamics
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D012097:Repressor Proteins