THE ATP-BINDING CASSETTE SUBUNIT OF THE MALTOSE TRANSPORTER MALK ANTAGONIZES MALT, THE ACTIVATOR OF THE ESCHERICHIA-COLI MAL REGULON

Transcription of the mal regulon of Escherichia coil K-12 is regulated by the positive activator, MalT, In the presence of ATP and maltotrio se, MalT binds to decanucleotide MalT boxes that are found upstream of mal promoters and activates transcription at these sites. The earlies t studies of the mal regulon, however, suggested a negative role for t he MalK protein, the ATP-binding cassette subunit of the maltose trans porter, in regulating mal gene expression. More recently, it was found that overexpression of the MalK protein resulted in very low levels o f mal gene transcription. In this report we describe the use of tagged versions of MalT to provide evidence that it physically interacts wit h the MalK protein both in vitro and in vivo. In addition, we show tha t a novel malK mutation, malK941, results in an increased ability of M alK to down-modulate MalT activity in vivo. The fact that the MalK941 protein binds but does not hydrolyse ATP suggests that the MalK941 mut ant protein mimics the inactive, ATP-bound form of the normal MalK pro tein. In contrast, cells with high levels of MalK ATPase show a reduce d ability to down-modulate MalT and express several mal genes constitu tively. These results are consistent with a model in which the inactiv e form of MalK down-modulates MalT and decreases transcription, wherea s the active form of MalK does not. This model suggests that bacteria may be able to couple information about extracellular substrate availa bility to the transcriptional apparatus via the levels of ATP hydrolys is associated with transport.