Model of specific complex between catabolite gene activator protein and B-DNA suggested by electrostatic complementarity.

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Abstract
Calculation of the electrostatic potential energy surfaces of Escherichia coli catabolite gene activator protein (CAP) dimer suggests a model for the complex between CAP and a specific DNA sequence. The positive electrostatic charge density of CAP lies on the 2 COOH-terminal domains and .apprx. 20-30 .ANG. from the molecular 2-fold axis. Assuming that the 2-fold axes of the CAP dimer and the DNA to which it binds are coincident, the positions of the positive electrostatic potential surfaces strongly suggest the rotational orientation of the DNA relative to the protein. A specific complex between CAP and its DNA binding site in the lac operon was built with the DNA in this orientation. The amino ends of the 2 protruding F .alpha.-helices interact in successive major grooves of the DNA. Four side chains emanating from each F helix can form H bonds with the exposed edges of 4 bases in the major groove. Electrostatic considerations and the necessity to make interactions between CAP and a DNA site as much as 20 base pairs long necessitate bending or kinking of the DNA. In this model of CAP complexed with B-DNA, as with those proposed for Cro and .lambda.cI repressors, the protruding 2nd helices of the 2 helix motif from both subunits interact in successive major grooves of B-DNA. Unlike Cro and similar to .gamma.cI, the protruding .alpha.-helices are nearly parallel to the bases, rather than the groove.