GENETIC STRATEGY FOR ANALYZING SPECIFICITY OF DIMER FORMATION - ESCHERICHIA-COLI CYCLIC-AMP RECEPTOR PROTEIN MUTANT ALTERED IN ITS DIMERIZATION SPECIFICITY

Many transcriptional regulators function in homo- or heterodimeric com binations. The same protein can carry out distinct regulatory function s depending on the partner with which it associates. Here, we describe a mutant of the Escherichia coli cAMP receptor protein (CRP) that has an altered dimerization specificity; that is, mutant/mutant homodimer s form preferentially over wild-type/mutant heterodimers. CRP dimeriza tion involves the formation of a parallel coiled-coil structure, and o ur CRP mutant bears an amino acid substitution affecting the first ''d '' position residue within the alpha-helix that mediates CRP dimerizat ion. The genetic strategy we used to isolate this CRP altered dimeriza tion specificity (ADS) mutant is generalizable and could be utilized t o isolate ADS mutants of other dimeric transcriptional regulators.