Growing Repertoire of AraC/XylS Activators

The AraC/XylS family of transcription activator proteins is defined by a 100-amino-acid region of sequence similarity (15) that forms an independently folding domain containing two helix-turn-helix (HTH) DNA binding motifs.A recent database search (http://hits.isb-sib.ch)(35) by the author using the AraC/XylS family profile (PS01124) (15) identified 830 family members!A number of AraC/XylS family members involved in carbon metabolism and responses to environmental stress have been intensively studied, including Ada, AraC, MarA, MelR, RhaR, RhaS, Rob, SoxS, and XylS (described below).More recently, several family members that regulate virulence factor expression in animal and plant pathogens have been well characterized.These virulence regulators are often part of complex regulatory schemes and are revealing new twists to regulation by the AraC/XylS family.Here I will briefly discuss some of the features of this large family and then focus on novel findings regarding AraC/XylS regulation of virulence factor expression, including those by Hulbert and Taylor in this issue (19a). STRUCTURE OF AraC/XylS FAMILY PROTEINSDetailed structures have been published for the AraC/XylS family domains of only two proteins, MarA and Rob (25,36).The backbone structures of these domains are virtually superimposable.The Rob structure exhibited an unusual interaction with DNA in which only one of the two HTH motifs made base-specific contacts with the DNA (25).However, the DNA interaction exhibited by MarA, in which each of the HTH motifs is inserted into an adjacent major groove of the DNA, appears to occur more widely (2,16,17,33,41).This interaction of each domain with two adjacent major grooves of DNA results in an unusually long binding site of 17 to 21 bp for each AraC/XylS family monomer.Most of the characterized family members function as transcription activators, although a few exclusively or additionally function as repressors (15).In addition to their DNA binding functions, at least some, and likely most, of the AraC/XylS family domains also contain transcription activation functions (3,4,21,22,24,29).Among the 830 AraC/XylS family members identified in the search described above, a large majority shared common protein architectures.These proteins have the family domain at the C-terminal end of an approximately 300-amino-acid-long protein that contains at least one additional domain.