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Science 23 June 1995:
Vol. 268. no. 5218, pp. 1721 - 1727
DOI: 10.1126/science.7792597
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Articles

Science, Vol 268, Issue 5218, 1721-1727
Copyright © 1995 by American Association for the Advancement of Science

articles

Crystal structure of lac repressor core tetramer and its implications for DNA looping

AM Friedman, TO Fischmann, and TA Steitz

Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8114, USA.

The crystal structure of the tryptic core fragment of the lac repressor of Escherichia coli (LacR) complexed with the inducer isopropyl-beta-D-thiogalactoside was determined at 2.6 A resolution. The quaternary structure consists of two dyad-symmetric dimers that are nearly parallel to each other. This structure places all four DNA binding domains of intact LacR on the same side of the tetramer, and results in a deep, V-shaped cleft between the two dimers. Each monomer contributes a carboxyl-terminal helix to an antiparallel four-helix bundle that functions as a tetramerization domain. Some of the side chains whose mutation reduce DNA binding form clusters on a surface near the amino terminus. Placing the structure of the DNA binding domain complexed with operator previously determined by nuclear magnetic resonance onto this surface results in two operators being adjacent and nearly parallel to each other. Structural considerations suggest that the two dimers of LacR may flexibly alter their relative orientation in order to bind to the known varied spacings between two operators.


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