A complex signaling module governs the activity of MalT, the prototype of an emerging transactivator family.

MalT, the specific activator of the maltose regulon, is the prototype of a family of high-molecular-mass ATP-binding bacterial transcription activators. On binding of its two positive effectors, the inducer maltotriose and ATP, MalT oligomerizes to an active state competent for promoter binding and transcription activation. In addition to its previously known DNA-binding domain, limited proteolysis showed that MalT contains three other domains, the boundaries of which were accurately delimited by N-terminal microsequencing. The N-terminal domain alone binds ATP. Maltotriose binding involves an extended region corresponding to domains 2 and 3, although weak binding to domain 3 alone was also observed. Moreover, maltotriose binding induces a conformational shift involving a movement of both domains 1 and 3 with respect to domain 2, leading to the active form of the protein. Sequence examination of the MalT homologues suggests that these three domains might constitute a signaling module.