Structure of the DNA-binding region of lac repressor inferred from its homology with cro repressor.

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Abstract
The amino acid sequence and the DNA gene sequence of the 25 amino-terminal residues of the lac repressor protein of Escherichia coli are homologous with the sequences of 5 DNA-binding proteins: the cro repressor proteins from phage .lambda. and phage 434, the cI and cII proteins from phage .lambda., and the repressor protein from Salmonella phage P22. The region of homology between lac repressor and the other proteins coincides with the principal DNA-binding region of cro repressor. In particular, residues Tyr-17 through Gln-26 of lac repressor correspond to the .alpha.-helix Gln-27 through Ala-36 of cro repressor, which is postulated to bind within the major groove of the DNA and to be primarily responsible for the recognition of the DNA operator region by the protein (Anderson, W.F. et al., (1981)). By analogy with cro repressor, it is proposed that residues 17-26 of lac repressor are .alpha.-helical and that this helix and a 2-fold-related .alpha.-helix in an adjacent subunit bind within successive major grooves of the lac operator, which is in a right-handed Watson-Crick B-DNA conformation. Also, by analogy with cro repressor, it is suggested that residues Thr-5 through Ala-13 of lac repressor form a 2nd .alpha.-helix and contribute, in part, to DNA binding. The proposed structure for the DNA-binding region of lac repressor is consistent with chemical protection data and with genetic experiments identifying the probable locations of a number of the residues of the repressor protein that either do or do not participate in DNA binding.