Crystal structure of LexA: A conformational switch for regulation of self-cleavage

LexA repressor undergoes a self-cleavage reaction. In vivo, this reaction r equires an activated form of RecA, but it occurs spontaneously in vitro at high pH. Accordingly, LexA must both allow self-cleavage and yet prevent th is reaction in the absence of a stimulus. We have solved the crystal struct ures of several mutant forms of LexA. Strikingly, two distinct conformation s are observed, one compatible with cleavage, and the other in which the cl eavage site is similar to 20 Angstrom from the catalytic center. Our analys is provides insight into the structural and energetic features that modulat e the interconversion between these two forms and hence the rate of the sel f-cleavage reaction. We suggest RecA activates the self-cleavage of LexA an d related proteins through selective stabilization of the cleavable conform ation.